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!
Well of course there is, that's why I try to sprinkle my weekly posts with comments on bird feeders, squirrels, novels I've been reading, and other escapades. This past week I happened upon a former colleague of mine who has taken this to new levels, much to my enjoyment.
We seem to be free of serious infectious diseases drama in the past week, unless you are a dairy cow.
Avian Flu
Initially only previewed in news reports and even now lacking details, one thing is clear: influenza A H5N1 infection in US dairy cows is much more widespread than previously revealed. We were surprised by this because asymptomatic infection is common and cow testing was only being performed in symptomatic animals. (This is reminiscent of the early days of covid!) The FDA and Department of Agriculture both report finding positive avian flu PCR tests in 1 out of 5 samples of pasteurized milk tested, although I can't find details about the total numbers and the geographic distribution of milk samples tested.
Of course, a positive PCR merely means that nucleic acid has been detected. It is highly likely that pasteurization inactivates H5N1 virus, and preliminary reports from FDA suggest this is true. Again, details are not available, but certainly no cause for panic about drinking pasteurized milk.
The take-home messages are clear: 1) H5N1 infection is highly prevalent in US dairy cow herds if 20% of all milk samples are PCR positive; 2) there is even more reason now to avoid ingestion of unpasteurized dairy products; and 3) USDA, FDA, and CDC are performing poorly in providing transparency and detailed evidence to the public. They say they are working on this, let's hope we see the fruits of that labor in the coming few weeks.
And, to give our federal agencies some credit, CDC has a spiffed-up web site for avian flu now, with weekly updates. Here's a quick view for the week ending April 20:
Note that this site deals only with human disease. If you want to get more on dairy cattle, you'll need to go to the USDA site. Here you can realize how geographically widespread the situation is.
USDA now has new guidelines for testing dairy cattle being transported interstate. Perhaps testing needs to be expanded beyond just interstate transport.
Covid Calm
Covid activity continues to fall, and weekly deaths now appear to be consistently less than 1000 even considering there is significant reporting delay for covid deaths. The vast majority are in the elderly.
Two new studies appeared highlighting covid vaccine side effects in children. One was a prospective cohort study utilizing insurance databases that likely carried some risk of classification errors because the authors did not perform any medical records review for verification. The study confirmed the known risks for myocarditis or pericarditis for ages 12 - 17 years with the Pfizer vaccine. Also, they found a possible safety signal for seizure occurring following both Pfizer and Moderna vaccination in 2 - 4 or 5 year-old children. This is pretty iffy; as they explained in the body of the text, it may simply be an artifact of how they defined the baseline seizure rate as a comparison number. This is worthy of further study, but in my opinion not something that should be put on the list of definite side effects yet.
The other study was a massive (3.9 million children) look at covid cases in California from 4/1/20 through 2/27/23, again using an administrative database. The article has too many explanatory graphs to show here, but the bottom line from the authors' predictive models suggests that vaccination prevented about 146,000 covid cases in 12 - 15 year-olds, 230,000 cases in 5 - 11 year-olds, and 168 hospitalizations in 6 - 59 month-olds. The authors did not find any association of vaccination with numbers of cases in the youngest age group, possibly because the numbers of vaccinated children were too small during the study period.
Our friends across the pond reported on various covid features from this past winter, November 2023 through March 2024. Results are based on self-reported data from a longitudinal survey study. Here are the main points:
An estimated 3.3% (2 million) of people living in private households in England and Scotland were experiencing self-reported long COVID (symptoms continuing for more than four weeks after a confirmed or suspected coronavirus (COVID-19) infection that were not explained by something else).
Long COVID symptoms adversely affected the day-to-day activities of 1.5 million people (74.7% of those with self-reported long COVID), with 381,000 (19.2% of those with self-reported long COVID) reporting that their ability to undertake their day-to-day activities had been "limited a lot".
Those in the youngest (aged 3 to 17 years) and oldest (65 years and over) age groups were the least likely to test positive for COVID-19 during the study period.
Those who have had a vaccination since September 2023 were less likely to test positive in the early waves of the study period (1 and 2); in later waves of the study period (3 and 4) there was no statistical difference.
Participants in the oldest and youngest age groups who did test positive in the study period were also less likely to report symptoms consistent with "influenza-like illness" compared with those in the middle age groups.
It's hard to find such recent data. I think this gives us a good peek at the future, assuming we don't have some major change in virus virulence or transmissibility.
Encouraging Progress in Malaria Prevention
I don't usually mention phase 2 trials because they are often much removed from clinical applicability and might change significantly once phase 3 trials are completed. This study is cause for optimism, so I'll break my custom here. Investigators in Mali performed the trial, part of which looked at 225 children randomized in equal numbers to a long-acting monoclonal antibody against Plasmodium falciparum with low dose, high dose, and placebo groups. Infection and clinical malaria was much less in the treatment groups.
The antibody is administered subcutaneously, a plus in resource-poor environments. If further studies confirm efficacy, this could save many lives.
Measles
No new cases were reported in the past week, good news though we know there will be more eventually. Also, I've been looking for more reliable assessments of worldwide activity and found another resource for Europe, the European Centre for Disease Control and Prevention. Updates appear only monthly. Here's what the most recent report, February, looked like:
Romania is the major hot spot, but note that many popular tourist destinations are represented. Here are current CDC recommendations that apply for all international travel:
Fiddlin' Will
By a happy occurrence in my web wanderings, I discovered a former colleague of mine was performing with his band, the Goldbug Revival, at a Salvadoran restaurant near my home. I crossed paths briefly with Will Sears when he was an infectious diseases fellow at NIH; he is now a medical officer at NIAID. However, in his "spare time," he is an accomplished musician. I was thrilled to see him on the fiddle and his wife Sarah singing lead at the band's first live performance and Sarah's first performance in front of a microphone ever. They were excellent!
See you next week. I'll be listening to some John Prine music in the meantime, waiting for Goldbug Revival's first album to drop. Prine was an early covid victim, dying in April 2020.
Bird flu has been in the headlines, accompanied by the usual extremes of concern levels. The past few weeks reminded me of Alfred Hitchcock's 1963 movie "The Birds," especially a diner scene where an elderly (my age?) amateur ornithologist (Ethel Griffies as Mrs. Bundy) attempts to explain why the "brain pan" size of a crow or blackbird makes any organized attack on humans impossible. The discussion is interrupted by another customer declaring the end of the world, interspersed with background shouts of orders for blood marys and fried chicken with baked potatoes.
Before we get to bird, a few other items of note.
Dengue Update
Maybe things aren't quite as bad, with a downward trend now apparent in the Americas.
The bulk of this atypical seasonality increase is from the Andean and Southern Cone regions of South America. Brazil by far leads the way, and Argentina, Peru, and Paraguay are in a second tier by numbers of cases. Here's a numbers breakdown for last week and for the calendar year as a whole:
Don't Dismiss Covid
Yes, the current variants and immunity levels in the US seem to result mostly in mild disease and numbers continue to trend downward, but we are seeing well over a thousand deaths per month from covid in the US. It is still a devastating disease.
No outbreaks in new jurisdictions in the US in the past week; Illinois and Florida still account for most of the cases this calendar year.
Highly Pathogenic Avian Influenza (HPAI)
The name itself is pretty ominous, cue those eery bird sounds from the movie. The biggest event last week was the confirmation of a case of influenza A H5N1 infection in a man from Texas, almost certainly acquired from the dairy cows he worked with. He was treated with oseltamivir and apparently is doing well. CDC issued a health advisory through their Health Alert Network last week, including a lot of good advice and helpful links. People who are around birds or dairy animals should take care; this includes those with backyard chicken flocks. The public health messaging has been pretty consistent: no cause for alarm, and certainly no reason to avoid dairy products or eggs at your local store (assuming the dairy products are pasteurized). FDA has a great Q&A page on this.
Note however that we have pockets of these viruses throughout the US, including in wild mammals.
We can be reassured that all of these strains are being tracked and sequenced worldwide through the Global Influenza Surveillance & Response System (GSAID). Scroll down at that link to watch an animation of the geographic spread of influenza A H5Nx viruses worldwide over the past few decades.
We have several antiviral therapies available, and vaccine prototypes are ready to enter mass production if necessary. So far, none of these strains seem well adapted for human-to-human spread, but if that happened it would be a major event that would cause much more concern. I'm also watching to see if this appears in pig populations, since swine flu viruses have been seen in the past to foreshadow human spread. Pigs have similar flu viral receptors to humans, so spread in pigs can be seen prior to a jump to humans. Thankfully, many of the events that facilitate spread among different animal species also are associated with lower virulence, so clinical impact is minimal.
Don't Look Up (Without Your Eclipse Glasses)
Yes, I know it's yet another movie. Just be careful with tomorrow's eclipse.
I actually had to pull out the lawnmower this week, to cut some weedy grass running amok in the yard. Nonetheless, I'm buoyed by the approach of the vernal equinox next Tuesday, the official start of spring. Winter will be done, and with it the winter respiratory viruses. They will reliably be replaced with spring respiratory viruses.
Here's a look at the pediatric infectious disease news the past week.
Details on the Failed GSK RSV Vaccine Trial
We've known for about a year that GlaxoSmithKline's RSV vaccine trial in pregnant people was stopped due to safety concerns: a higher rate of preterm births in the vaccine group compared to placebo. Now we have more details, similar to what was reported to FDA and shared in various meetings. Preterm birth rate was 6.8% (237 of 3494 infants) in the vaccine group and 4.9% (86/1739) in the placebo group; it was statistically significant. Neonatal mortality was higher in the vaccine group, 0.4% versus 0.2%, but did not reach statistical significance.
On the other hand, vaccine effectiveness was pretty good:
The currently approved maternal RSV vaccine from Pfizer also had a hint of a safety signal for preterm birth, less so than the GSK product, and these signals combined resulted in the Pfizer vaccine being approved for a later time in gestation, at 32 weeks at the earliest. Postmarketing surveillance is ongoing. Perhaps the most difficult part of assessing this safety signal is whether it is real or not. We are lacking a key factor in making this assessment: biologic plausibility, i.e. the mechanism by which these vaccines might cause preterm birth. Without that, it is still possible this represents just a chance observation. From my perspective, I would still encourage RSV vaccination for pregnant people as well as nirsevimab therapy for at risk infants born to unvaccinated mothers. We have time for more discussions of any new data prior to our next RSV season this fall.
Waterborne Disease Outbreaks Associated With Drinking Water
I'm a big fan of CDC's Surveillance summaries, and this one published last week is of interest. The report concerns 214 outbreaks from 2015-2020. I wasn't thrilled to see my home state represented prominently.
Outbreaks occurred year-round, and biofilm exposures predominated.
In case you aren't familiar with biofilm-associated outbreaks, here's the quick explanation from the text:
"...microbial communities that attach to moist surfaces (e.g., water pipes) and provide protection and nutrients for many different types of pathogens, including Legionella and NTM [non-tuberculous mycobacteria]... Biofilm can grow when water becomes stagnant or disinfectant residuals are depleted, resulting in pathogen growth... Furthermore, biofilm pathogens are difficult to control because of their resistance to water treatment processes (e.g., disinfection)... Exposure to biofilm pathogens can occur through contact with, ingestion of, or aerosol inhalation of contaminated water from different fixtures (e.g., showerheads) and devices (e.g., humidifiers)..."
Not to minimize the severity of these events, but I couldn't help thinking about a whole new version of Hitchcock's Psycho shower scene based on this.
Legionella was by far the most common pathogen. The report has detail on every outbreak by year and location, as well as a listing of contributing factors. It's a great roadmap for future prevention.
Measles (Again)
It seems like I could devote every week's post entirely to measles and not run out of things to say. Here's the current US situation.
As I've stated previously, it's the sheer number of unconnected sites that concerns me now. Let's put this into some perspective.
As of March 14, we have 58 cases reported from 17 jurisdictions. In all of 2023, we had the same number, 58, reported from 20 jurisdictions in the US. So, we're way ahead of the game for recent years, but we're also not breaking any records compared to pre-pandemic times.
Looking more closely at the 2 biggest years recently, the 2014 (and somewhat 2015) numbers had a large contribution from a single site, Disneyland. More impressively, the 1274 measles cases in 2019, the highest number in the US since 1992, largely involved orthodox Jewish communities in New York - relatively epidemiologically isolated communities with very low immunization rates. A CDC update in fall 2019 (I couldn't find a final tally) stated that 75% of cases for the entire country that year originated from these communities.
Fingers crossed that we don't eclipse the 2019 figures this year, but with reduced vaccination rates and already widespread measles transmission occurring, it doesn't look good. We're just now coming to the spring break and summer travel season - importation of measles from travelers has been a large contributor to US measles outbreaks in the past.
Pediatric Covid ICU Admissions
A recent report of registry data from 55 hospitals during the first almost 2 years of the pandemic showed that about 8% children <21 years of age admitted to intensive care with covid had immunocompromising conditions (ICC). Secondary bacterial infection was more common (9.5% versus 7.3%) and mortality (11.4% versus 4.6%) was higher in the ICC group.
That Pesky Flu
The map is getting a little greener, apropos of springtime. Note in the link you can animate the map to show progression from the fall to the current week.
Better seen here, we did experience a little pause in our decrease of ILI, now headed down but at 3.7% still above the official "epidemic is over" mark of 2.9% for this year.
Any Chipmunk Sightings?
My 2024 Farmer's Almanac says that the real harbinger of spring in the eastern US is the appearance of the eastern chipmunk (Tamias striatus) above ground. As opposed to their squirrel brethren, chipmunks at my house don't bother my bird feeder, so I'm OK with them. I learned that although they stay below ground for the winter, they aren't true hibernators but rather experience torpor. They may sleep for several days in their bedrooms, followed by a trip to the underground pantry for snacks. Sounds like a good plan for retirement.
