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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?

Not only did the summer solstice arrive June 20 as expected, the temperatures outside confirm that summer is here. I noted 100 F in the shade on my patio Saturday afternoon.

Summer usually means a switch in circulating pathogens and pediatric infections. Outdoor activities mean more scrapes and scratches which then means more cases of cellulitis, abscess, and osteomyelitis. Also in the mix are the vector-borne infections including Zika, Powassan, and West Nile viruses, babesiosis, Lyme disease, Rocky Mountain spotted fever, and yes, even in the US, malaria and dengue. International travel lengthens the list considerably.

Respiratory viruses usually take time off in the summer, other than enteroviruses - the name misleads many to conclude these are primarily GI pathogens, but in fact they are more likely to cause mild respiratory illnesses. They do replicate in enterocytes and the viruses are found in stool, hence the name. Peak enteroviral season usually is August and September, though they are present year-round.

That said, let's look at a few out-of-the-ordinary pathogens to watch for this summer.

Summer Covid?

Yes, I know I'm repeating myself, but it's again worth noting that our ability to monitor SARS-CoV-2 is in a new era. With the pandemic ended and little to no availability of free testing, plus local, state, and federal jurisdictions relaxing reporting requirements, we're mostly down to crystal ball guidance to know when to expect the next surge. The closest to an accurate predictor is waste water monitoring, though it too is limited. Here's the latest:

You can see the start of an upward blip maybe - looks a lot like last year when we had a mini-surge that peaked in September and seemed to correlate with clinical disease. Levels are low now. Test positivity is up a little out west.

CDC's Advisory Council on Immunization Practices meets this week, June 26-28, with covid vaccines discussed Thursday morning and voted on Thursday afternoon.

Summer Bird Flu?

Still not a major worry for us, other than folks who have contact with live poultry (included backyard coops), other livestock, and unpasteurized dairy products. Still, it's good to have a plan for when and how to evaluate potential cases if they show up on your doorstep.

If you are seeing a child with a cold this summer (remember, so far the 3 cases of AH5N1 in the US have been mild and include conjunctivitis), please add in a few questions: any exposure to livestock, or to others with this exposure - this includes those state fairs with petting opportunities; also ask about unpasteurized dairy ingestion. If the answer is affirmative, this is someone worth testing for influenza, and if positive for influenza A in the summer in the US should launch more investigation that will involve your local health department.

Fortunately, CDC has lots of helpful advice at the Bird Flu web site. Scroll down to the Recommendations for Clinicians. The weekly update doesn't contain significant new actionable information. Other pages are in the process of being updated, but again your local friendly ID doctor or local health department are good partners to help you.

Summer Reading?

Not a summer pathogen, but will be occupying some of my time the next few months. Many of you probably would surmise that Dr. Fauci's new book is high on my list, but in fact it's not. I lived through all of this, plus I'm much more interested in the science than the politics. I'm sure it will be a bestseller, and I'm appalled at the ongoing vilification and threats he's experienced.

My biggest summer reading project is Emily Wilson's new translation of The Iliad, but it's not really a beach book in spite of the seas and beaches mentioned in the epic. For my annual beach trip I'll instead be buried in noir mysteries and other enjoyable light reading.

Romare Bearden's Odysseus Enters at the Door Disguised as an Old Man, c. 1977, from https://www.nga.gov/learn/teachers/teaching-packets/bearden.html.

My long-suffering (try putting up with me for 40+ years) wife, a retired general pediatrician, thought my posting about the FDA VRBPAC meeting was a bit too detailed for front-line healthcare providers. Reading it again, she's right, but of course I'll push back a little bit given that FDA has backtracked on the committee's recommendation. First, a few other updates.

Wild-type Polio Update

Thankfully we haven't had any recent polio appearances in the US, but it's a bit discouraging to see what's going on worldwide. The Global Polio Eradication Initiative reported 1 case of wild-type polio in each of 2 countries, Afghanistan and Pakistan. Here's the complete list for the week which includes vaccine-derived cases and environmental sampling as well:

  • Afghanistan: one WPV1 case
  • Pakistan: one WPV1 case and 20 positive environmental samples
  • Côte d’Ivoire: three cVDPV2-positive environmental samples
  • DR Congo: one cVDPV1 case
  • Ghana: one cVDPV2-positive environmental sample
  • Liberia: four cVDPV2-positive environmental samples
  • Niger: one cVDPV2-positive environmental sample
  • Sierra Leone: six cVDPV2-positive environmental samples
  • South Sudan: one cVDPV2 case
  • Yemen: three cVDPV2 cases

Remember that paralytic polio cases represent only the tip of the iceberg for polio infections; the vast majority of infections are asymptomatic, with a few percent manifesting as nonspecific febrile illnesses. Paralytic polio cases comprise less than 1% of infections. So, the appearance of 1 case can imply that at least 100 more infections were present in an area.

Can Infants Spread C diff in Households?

Asymptomatic Clostridioides difficile carriage is common in infants, and the organism seldom causes illness under 2 years of age. That's why you don't want to test for C diff in younger children. An interesting new study suggests, but by no means proves, that these asymptomatic carriers might be the source of household spread which could include spread to more vulnerable individuals.

Thirty families were recruited at their child's 4-month checkup to participate in this longitudinal study where participants mailed soiled infant diapers every 2 weeks to the study site, until the infants reached 8-9 months of age. Rectal swabs from mothers, and sometimes from fathers, were mailed at the same time but in separately sealed containers. (Sorry, but I couldn't help but wonder if the mail carriers had to put up with some unusual package odors!) The specimens were tested for C diff and positive samples were strain-typed and tested for toxin production.

Probably the researchers would have needed to perform more frequent sampling to prove the directionality of transmission, i.e. infant to adult or vice-versa, but they did note that the adults, compared to the infants, seldom were the initial positive carriers in these families. Sharing of C diff strains in the families was common and more often implicated infant to adult directionality. C diff prevalence in infants was 50.0-71.4%, including nontoxigenic strains, while maternal positivity was 20.0-40.0% and fathers were 20.0-37.5% positive. None of the infants or parents developed symptoms.

Something to keep in mind, but please don't start testing infants for C diff.

Misinformation Tracking

A recent article tried to look at patterns of misinformation and flagged content on Facebook. Unfortunately subscription is required for full article access, but the abstract is an accurate summary. Based on numbers of pageviews, the authors felt that unflagged content on Facebook was more likely to be influential.

The authors used a complicated (to me) combination of crowd-sourcing and machine learning to derive estimates of vaccine hesitancy and matching to pageviews. They concluded "...We estimate that the impact of unflagged content that nonetheless encouraged vaccine skepticism was 46-fold greater than that of misinformation flagged by fact-checkers." This unflagged content predominantly consisted of real facts, e.g. rare deaths following vaccination, that then were misinterpreted by viewers as the vaccine causing the death rather than within the expected death rate based on the general population, regardless of vaccination status. A classic misinterpretation due to lack of a control group!

Along the same lines, I noted with sadness that the Stanford Internet Observatory that tracks misinformation is shutting down, in large part due to lawsuits and online attacks received by staffers. Enough said.

The Flu Front

Not to be overly concerned, but a brief CDC report demonstrated spread of neuraminidase mutations in influenza A H1N1 strains in the US, showing reduced susceptibility to oseltamivir. We'll hope these don't become more common.

On the positive side, a NEJM article demonstrated that heat readily inactivates the current influenza A H5N1 strains showing up in cows' milk. I didn't see any earth-shattering news on H5N1 in the past week, but I happened upon the AAP Red Book's outbreak pages for the topic and really liked their bullet summary for current status in different populations:

People: 3 cases (in 2024)
Person-to-person spread: None
Current public health risk: Low
Dairy Cows: Ongoing multi-state outbreak
Wild Birds: Widespread
Poultry Flocks: Sporadic outbreaks
Mammals: Sporadic infections

Apparently these outbreak pages are free to the general public, so check it out. (IMHO every pediatric healthcare provider should have a Red Book subscription, included in AAP membership.)

Covid Vaccine Backtracking

Initially following the FDA VRBPAC meeting on June 5, FDA recommended that the JN.1 covid strain be utilized in the next iteration of covid vaccines. On June 13 they amended this, stating that "if feasible" the KP.2 subvariant should be used instead. What's going on?

After a day-long discussion, the VRBPAC members were asked to vote on whether or not to choose a monovalent JN.1-lineage strain to use in the next vaccine. The vote was unanimous in favor of this. As seen in the section of the lineage chart below, the JN.1 lineage includes that purple JN.1 strain at the left, as well as all the subvariants derived from it.

The VRBPAC vote didn't specify which of all those strains to pick. The discussion following the vote did address that, with the important concerns being whether newer subvariants like KP.2 and KP.3 might be dominant this fall and could evolve further to be more antigenically distinct than JN.1. In that scenario, a JN.1-based vaccine might be less effective. On the other hand, KP.2 might prove to be a worse choice if its derivatives became more antigenically distinct from other subvariants that might predominate in the fall. This is too tough to predict now. (I was also interested that CDC stated they aren't emphasizing research on using generative artificial intelligence as a predictive tool.)

I was monitoring the VRBPAC meeting in real time, and it was clear that Dr. Peter Marks, director of the FDA's Center for Biologics Evaluation and Research, leaned more towards using the KP.2 subvariant, and I guess eventually this view prevailed. I'm not quite clear why the initial guidance didn't say that since I don't see any startling new information this past week. Here's the latest variant picture from the same link as above.

As always, the last 2 fortnight periods are only estimates; in the past, these estimates have been fairly accurate predictors. The 6/8/24 bar isn't that different from 5/25/24 in that KP.2, KP.3 and LB.1 seem to be trending towards dominance while JN.1 itself fades. It's important to remember that in general across the US covid activity is pretty low, with a few spots of minor uptick but nothing approaching a big surge so far.

Shifting towards the KP.2 variant as the vaccine component won't affect the Moderna and Pfizer planning, they were already working on both JN.1- and KP.2-based vaccines. However, Novavax won't be able to supply a KP.2 vaccine for another 6 months. They would however be able to have a JN.1 vaccine by fall. That "if feasible" phrase in the FDA announcement seems to leave the door open to allow Novavax to continue with JN.1 vaccine production; the company submitted an FDA application for authorization of this vaccine on June 14, the day after the new FDA announcement. I'll be interested to see how the discussion goes at the CDC ACIP meeting in a couple weeks.

The Eight Queens Puzzle

I was looking up the term backtracking to see where it came from (apparently it showed up in 1870), but instead found another use of the term in computer science, specifically computer algorithms. That led me to the eight queens puzzle.

Apparently there are 92 separate solutions to this puzzle, first published in 1848. Subsequently the puzzle was expanded to all natural numbers, the n queens puzzle, for which solutions exist for all of them except the numbers 2 and 3. The chessboard then has n rows and columns. This is a dangerous rabbit hole into which I hope I never fall.

Happy Father's Day to all you dads, granddads, step-dads, and every other iteration!

The title above is one of several great turns of phrase in the book I just finished reading, Edith Wharton's Age of Innocence. It refers to an episode where the protagonist was at a loss for words during a poignant encounter and presumably only later thought of something better to have said. I've been there.

Next Round for Covid Vaccine

The FDA's Vaccine and Related Biological Products Advisory Committee finally had their meeting last week; it had been postponed to give a little more time to see which way the new SARS-CoV-2 variants were headed. I was able to listen in on most of the meeting and have reviewed all the documents. The vote was unanimous to choose a monovalent JN.1-based vaccine for the next iteration, no surprise and in agreement with the recent WHO decision I discussed recently. (For those interested, there is quite a bit of international collaboration on these types of decisions. See the ICMRA posting about covid vaccines.) Still, there were some interesting updates on covid in general. I'll try to distill this down into the main takeaways.

The Latest on Epidemiology (from Thornburg FDA presentation)

Current circulation of SARS-CoV-2 is relatively low. Although our reporting is not as reliable these days, looking just at percentage of positive covid tests in orange you can see we are in a lull now, though perhaps with a hint of an uptick. This is pretty similar to last summer when we saw a bit of a surge in summer into fall and winter. SARS-CoV-2 still has not come around to a winter seasonality seen with other coronaviruses of with influenza, making predictions for surges and vaccine composition very tough.

JN.1 lineages replaced XBB.1.5 lineages during winter 2023-2024. I like the depiction below because it's looking at normalized numbers of positive tests rather than a percentage of positive tests due to different variants. This gives a better appreciation of numbers of cases and shows that we are still talking about relatively low numbers compared to 2022.

Here's a closeup of the most recent part of the above slide showing that KP.2-like, KP.3, and other JN.1 derivatives are starting to take over, though still all at very low numbers.

The recent subvariants have very few differences from other JN.1-derived strains and antigenically are very similar. This has important meaning for vaccine choice - should it be the original JN.1 variant or one of these newer KP.2 or KP.3 type subvariants, currently at extremely low numbers? Look at the last 2 rows in the table below, showing that these newer subvariants have very few mutation differences from the earlier JN.1-like variants.

In a totally new and as yet unpublished CDC analysis, severity of JN.1 infections does not appear to be worse than earlier lineages. The trend was towards milder illness, though not statistically significantly different. Note these numbers are just for adults.

Vaccine Effectiveness in Children (from Link-Gelles FDA presentation)

This it tough to estimate because children generally have milder disease, plus so few children are vaccinated. Adult data is pretty favorable for VE; SGT failure is a faster method of testing and correlates will with JN.1 lineage strains. 2023-2024 VE drops a little with these strains compared to effectiveness against XBB lineage strains.

On the pediatric side, it's important to remember that the vast majority of US children have been infected with SARS-CoV-2 at some time in their lives - this has been apparent since late 2022.

So, it's important to determine any VE now in light of prior infection and vaccination. We can't rely on older estimates. Here's the best and latest estimates for VE in children who received vaccine in the past year. Confidence intervals are relatively wide, reflecting the small numbers able to be studied, but do show benefit in prevention of ED or urgent care use. VE wanes with time after vaccination as it does with all age groups, but there is clear benefit for covid vaccination of children.

David Wentworth, representing WHO, delivered a wonderful explanation of the complexities in choosing among current subvariants for vaccine inclusion. He had this great quote: "... antigenic evolution just speeds up waning immunity." The variant evolution we're seeing now is parallel, i.e. lots of different subvariants evolving on their own, in parallel, rather than one subvariant evolving into another, and then into another, etc. Parallel evolution is what XBB lineages did previously, and we're seeing it now in the JN.1 groups. The slide below demonstrates this process with a timeline on the X axis.

The dilemma in choosing composition of the next vaccine is that no one knows which way the very new subvariants will evolve in terms of antigenic similarity to earlier JN.1 strains. Currently, KP.2, KP.3, and JN.1.23 are within what is thought to be close proximity to JN.1 in terms of antigenic similarity and therefore a vaccine based on any of those likely will have cross-reactivity with one another, enough to provide protection. However, as illustrated by the arrows, it just isn't known how the offspring of the newer subvariants will evolve - will it be farther away from JN.1 and each other, or will it remain relatively stable?

No one can predict what next fall's or winter's subvariants will look like. Once they appear, new lab testing would need to be done, ideally using human serum containing antibody to the newer strains, which Wentworth stated would take about a month to produce. So, it's not something that can be turned around quickly.

Also, it bears mentioning that virtually all of the immunity studies involve neutralizing antibody. Antibody does correlate well with VE, but T-cell immunity also is important. We don't see as much data about this arm of the immune system because the studies are more difficult.

All 3 US vaccine manufacturers, Moderna, Pfizer, and Novavax, presented their new data at the meeting. They are developing and testing new vaccines "at risk," meaning the companies are making vaccines without funding currently, risking their own research and development dollars, hoping whatever they are working on will be recommended for the next covid vaccine rounds and allow them to recoup their investment. Moderna and Pfizer have both developed JN.1- and KP.2-based mRNA vaccines. Novavax, the adjuvanted protein-based vaccine, only developed a JN.1-based vaccine. The protein vaccine takes much longer to construct than do mRNA vaccines, about 6 months to get good data in all. So, if a KP.2 or other vaccine were recommended, Novavax would need to start over and wouldn't be ready until about December.

I don't usually like to use pharma slides to illustrate points, but this one from Pfizer isn't biased in favor of their product and I think nicely shows the current situation, including how closely related the newer subvariants are to JN.1.

In the discussion after the vote to have a monovalent JN.1-based vaccine, which could mean one based on KP.2, the majority of the group felt that using the JN.1 variant rather than KP.2 or another subvariant was the best route, both to allow Novavax to be ready this fall but also not to take a chance that fall and winter predominant subvariants might be more antigenically removed from KP.2 antigenically. All in all I felt this was the right choice, though I probably wouldn't have let Novavax's problems affect the decision; very few US residents have received Novavax in the past, though it is nice to have an alternative to mRNA vaccines available.

On June 7 the FDA formally recommended sticking with the JN.1 strain for this next vaccine round. Next step with be the CDC's Advisory Council on Immunization Practices meeting the end of this month, where the official seal of approval will be issued. I'm sure Moderna, Pfizer, and Novavax already are ramping up production.

NASEM Long Covid Report Available

Long covid remains a quagmire, lots of different symptoms, many of which are vague, and still no definite light shed on diagnosis and treatment of what is likely a heterogenous group of conditions requiring different approaches. The National Academies of Science, Engineering, and Medicine published their full report, available free online. I haven't gotten through all of it, it's pretty long, but it is of interest to those practitioners who see these patients. Most of the evidence is from adults, but it appears that pediatric patients tend to have a better prognosis, especially if improvements are occurring in the first year after onset. Note that a positive covid test is not required for diagnosis testing may not have been done at the time of the triggering infection and antigen or PCR tests will have reverted to negative by the time a long covid diagnosis is considered.

Doxycycline for Post-Exposure Prophylaxis of STIs

The official guidelines appeared this past week, although the gist of the recommendations had been floated previously. Particularly high risk groups are gay, bisexual, and other men who have sex with men and transgender women. The summary is very helpful for practitioners who may want to print out and post Box 1 and Box 2 in their workspaces. Note that the recommendations apply just to those high risk groups.

Summer Bugs!

Bugs in the sense of both insects and microbes. We now have more details about a new rickettsial agent, termed species C6269, that caused a Rocky Mountain Spotted Fever-like illness in 2 individuals in northern California last summer. Both had severe disease, were hospitalized and treated with doxycycline, and survived. As always, keep RMSF and other tick-borne diseases in mind during our warm months.

Speaking of bugs, our dog came down with a skin abscess, expertly debrided by her veterinarian. She is now enjoying chewable amoxicillin/clavulanate but is less thrilled with her "cone of shame." The vet had another bug concern, however. She didn't want the dog to spend much time outside - apparently it is also maggot season, and they love open dog wounds. The vet doesn't know I'm an ID doctor, and I was trying to come up with some clever comment on maggots but failed at that moment - belated eloquence of the inarticulate!

Courtesy of Wikipedia. Hope you aren't eating as you read this.

2

We've had a slow week of infectious diseases events, but that hasn't slowed down the chatter and noise. I've tried to distill out the more important topics this week.

The Covid Front

Even though US tracking systems have been greatly dismantled in many states, I can still safely say we are in a lull. Naturally, thoughts turn to predicting the next surge and how to mitigate it.

I mentioned in my May 5 post that the FDA's Vaccines and Related Biological Products Advisory Committee meeting to decide on composition of the next iteration of covid vaccine would be held on May 16 and likely would make the same decision as the WHO already has, using the JN.1 variant. However, they suddenly postponed this meeting to June 5. FDA didn't offer an explanation for the postponement, but the last-minute change leads me to suspect that they wanted a little more time to think about newer variants with possible significant differences in immune-escape properties. Here's a deeper dive into that.

As you can see in this latest CDC variant report, the dark purple JN.1 proportion is decreasing, with KP.1 and KP.2 starting to expand. Both of those are in the JN. 1 lineage:

All of the JN and KP variants are informally called FLiRT variants, an easier shorthand than trying to remember all the letters and numbers. It stands for amino acid substitutions, in this case phenylalanine (F) substituted for leucine (L) in the 456 position (F456L) and arginine (R) to threonine (T) in the 346 position (R346T) in the spike protein genomic code. These 2 mutations are in antibody binding sites that neutralize the virus, and the mutations make SARS-CoV-2 less vulnerable to vaccine- and infection-acquired antibodies. A JN.1-derived vaccine likely would offer some protection, but perhaps by the June meeting we'll know a bit more about all of this. If they do recommend using KP.2 instead of JN.1 for example, I don't think there would be a significant delay in mRNA vaccine production by Pfizer and Moderna, but it might cause problems for other vaccine platforms such as the one used by Novavax, the other approved vaccine in the US which is an adjuvanted protein subunit vaccine. I'll be watching as much of the June 5 meeting as I can.

HPAI

Now we have a grand total of 2 people in the US infected this year with Highly Pathogenic Avian Influenza, along with a lot of cattle and other animals; a recent MMWR provides details. The new, improved CDC website has lots of helpful links. The second case, in Michigan, was similar to the first human case of A H5N1 infection in Texas - very mild illness with conjunctivitis as the primary symptom. This strikes me as very unusual for evolving epidemics in that usually the more severe cases are identified first because they are more likely to come to medical attention. Both of these cases were identified through surveillance of dairy workers which suggests to me that currently HPAI in humans is a very mild infection, possibly with high rates of asymptomatic infection. This is a good thing generally, but also problematic for tracking infection rates. The MMWR reports only 350 exposed dairy workers are being followed, a very small number. Ideally we'd have more tracking of cattle and dairy workers, regardless of illness or exposure to infected animals. Getting cooperation from dairy farms will be difficult, we're talking about livelihoods in an industry where a shutdown for a cow outbreak could send someone into bankruptcy.

I'm watching multiple feeds to keep up with all of this. A report in NEJM last week was encouraging - heat inactivation of spiked milk samples significantly lowered infectivity in mice fed the milk.

Also in the good news department, USDA reported preliminary findings on HPAI detection in muscle tissue of culled dairy cows. 95 of 96 samples tested so far were negative by PCR. Note that these were condemned animals, none of the meat entered the food supply.

On the somewhat negative side, more cattle herds have been hit with the virus, according to USDA.

Poultry outbreaks also continue with Minnesota registering more detections last week. Note that backyard flocks are not immune to HPAI.

On a slightly related topic, I was disappointed but not surprised to learn that the World Health Assembly, the decision body for the WHO, removed a pandemic preparedness treaty that was to be discussed at their meeting starting May 27. It appears that political considerations caused the cancellation; much misinformation is circulating, especially in the US. The treaty would help countries design programs for pandemic preparedness and in no way allows the WHO to control countries' own public health programs as claimed by some sources.

Potpourri

A scattering of reports might be interesting for readers. First, beware of undercooked bear meat. Six out of eight people who consumed undercooked, previously frozen black bear meat developed trichinellosis. Freezing doesn't kill Trichinella parasites. Beware the (undercooked) bear.

CDC released a Health Advisory Network alert for meningococcal disease in Saudi Arabia, although this is pretty much routine for this time of year during religious pilgrimage season. Travelers to the region should be immunized for meningococcal disease, which is more easily transmitted in the crowded situations during Islamic pilgrimages to Mecca.

Speaking of Noise

I'm pretty sure I've never mentioned this in the blog, probably because I'm so embarrassed, but I'm a 2-time harmonica school dropout. This last exit was due to a combination of my inability to master bending notes on the diatonic harmonica and the fact that my dog runs away from me every time when she hears my mellifluous tones. I've now solved the second problem by clearing a practice space in my trash-heap of a basement where the dog can't hear me, but bending will still be a challenge. It's a technique to hit notes that are in between standard notes; there are maybe hundreds of online instruction sites for how to form your mouth to do this, but basically it's just trial and error and takes several months for most people.

Graphic courtesy of Luke.

Maybe by announcing my intentions I'll be shamed into pulling it together this time and can return to harmonica school. I can't promise to report on my progress, especially if I have none!