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The shootings in Pennsylvania give all of us a chance to reflect. We should be thankful that more people weren't harmed while also keeping the families of the critically injured and the dead close to heart.

More Poultry Workers Presumptively Infected With Bird Flu

The Colorado state health department now reports 3 other presumptive H5N1 cases in poultry workers, adding to the single case in that state earlier this month. All apparently had mild illness with respiratory symptoms and conjunctivitis. We're still waiting for ongoing studies to provide better understanding of transmission modes and extent of infection in high-risk workers; such knowledge likely will lead to effective preventive measures.

Infection in animals is widespread in the US.

Olympic Wastewater

The World Health Organization has plans to monitor 6 pathogens in wastewater from the 2024 Olympics and Paralympics in Paris: poliovirus, influenza A and B viruses, mpox, SARS-CoV-2, and measles. It's an interesting read if you have the time.

More Kudos for Nirsevimab

Last week saw the publication of a report from France of a matched case-control study of nirsevimab effectiveness during the 2023-2024 RSV season and reflects real-world implementation as it occurred in that country. Results were again excellent, 83% (95% CI 73.4-89.2%) effective against hospitalization.

Returning to my broken record mode, I implore all pediatric healthcare providers to ensure families protect their infants with nirsevimab (or with maternal RSV vaccine use).

Blood Culture Bottle Shortage

Usually we worry about medication/vaccine shortages, but don't forget equipment shortages are relatively common. Now the FDA has announced a shortage of blood culture bottles likely to last a long time. This does give me an opportunity to reference again one of my favorite guidelines, recently updated, concerning effective use of the microbiology laboratory.

Many providers were surprised by the recommendations for volume of blood to be drawn for pediatric blood cultures:

Two separate cultures are usually recommended but can be drawn at the same time. Utilizing appropriate skin decontamination and proper blood volumes will increase yield of true pathogens. While one could argue that adhering to the guidelines above would actually increase the number of bottles used (since most pediatric practitioners obtain just 1 culture at a time), I'd push back against that claim by stating that fewer bottles would be used because we wouldn't be obtaining cultures in very low risk clinical settings nor chasing contaminants nearly as often. If you frequently make decisions on obtaining blood cultures, this is a good time to review the guideline section on bloodstream infection.

Remember the Children

I wrote some time ago about how the assassination of President Kennedy in 1963 affected me. I was a 5th grader when the presidential motorcade, including the limousine carrying JFK, the First Lady, and Texas Governor Connally and his wife, drove past my school the day before the assassination. I was one of a couple hundred kids on the curb waving as they went by. I remember the confused thoughts in my 10-year-old mind. Take time to discuss yesterday's event with your children, grandchildren, and with your patients and their families.

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.

Yes, summer doesn't officially begin for almost another 3 weeks (June 20, 4:51 PM EDT is summer solstice where I am), but it's a relatively stagnant time for infectious diseases now. It's sort of nice to view the maps and graphs right now. Just bask in the green of influenza-like activity:

I've mentioned recently that covid and other tracking systems are now ramped down in many jurisdictions, so we're mostly back to crystal ball predictions. Wastewater data, now including influenza in addition to SARS-CoV-2 and mpox, can be helpful in anticipating disease surges, but as you can see in the example below for influenza A, we have almost no data for most of the country - the gray dots aren't reporting.

And, speaking of flu ....

Avian Flu

If you aren't in close contact with fowl (includes backyard poultry aficionados) or cattle, you don't have much to worry about influenza A H5N1. Still, we did see our third human case in the US last week, this time from another dairy farm worker in Michigan who was exposed to infected cows. Symptoms seemed mild but were slightly different from the 2 previous cases that only had conjunctivitis. This third individual complained of cough and eye discomfort with watery discharge and was afebrile. He was treated with oseltamivir.

Front line clinicians assessing anyone for respiratory illness, including conjunctivitis, should ask about close contact with sick or dead animals, particularly wild or domestic birds, wild mammals, and domesticated animals including cows.

The World Organisation for Animal Health now lists 26 different groups of animals confirmed positive for avian influenza A H5N1 across the US:

Wild animals: coyote, Virginia opossum, feral cat, gray seal, bobcat, Mephitidae unidentified (includes skunks and stink badgers), striped skunk, American mink, tiger (where was a wild tiger in the US?), harbor seal, northern raccoon, puma, bottlenose dolphin, American black bear, brown bear, polar bear, red fox, Amur leopard (again, in the wild in the US?), fisher, American marten, and Abert's squirrel

Domestic animals: Camelidae (alpacas in this instance), cat, goat, cow

Also, ingestion of unpasteurized dairy products is a risk factor for mammals, likely including humans. So far it isn't entirely clear whether ingestion of raw beef is a risk factor, but good to ask your patients about. Anyone with a risk factor should undergo influenza testing and, if positive especially this time of year get help from your local health department.

If nothing else, I learned about a few new (to me) animals from investigating the WOAH list. Thank goodness for Wikipedia.

Looking Ahead

The postponed FDA VRBPAC meeting to advise on composition of the next covid vaccine is still scheduled for June 5. Pertinent meeting materials usually appear on the website a day or so before the meeting, but nothing so far to tip FDA's hand on which variant(s) will be included in the next iteration.

In the meantime, enjoy the doldrums!

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!