vaccination – Pediatric Infection Connection

The Wiedermann Thanksgiving Massacree of 199?

Bud WiedermannNovember 24, 2024November 24, 2024Leave a comment

Thanksgiving week has arrived, which for me means making checklists and time schedules and then revising them several times up until Thursday, at which point nothing happens according to schedule and I just go with the flow. It's also a time I remember the infamous Wiedermann Thanksgiving Massacree of 199? (I can't remember the exact year), with apologies to Arlo Guthrie.

Understandably in the past few years, this blog has drifted to the latest public health and epidemiologic trends, but I'm comforted by the fact that respiratory infections remain relatively calm and that this past week's publications allow me to focus more on recent original studies of interest to pediatric healthcare providers and the general public.

Macrolide-resistant Mycoplasma pneumoniae

I'm getting pretty tired of hearing about our resurgence of "walking pneumonia," but this article caught my eye. It's a report from North Dakota, and my interest wasn't in the fact that the investigators found evidence of macrolide resistance; that's nothing new. The bigger question is whether the resistance has major clinical significance. I've stated previously that, because Mycoplasma lower respiratory infection is largely a self-limited disease, it's difficult to know whether antibiotic treatment helps, and if it does, whether the amount of benefit is worth treating with antibiotics. The vast majority of "walking pneumonia" cases in children don't need any nasal swab or radiographic testing, nor any treatment.

The study was small, just based on 10 children of which 8 had macrolide resistance genes detected in their nasal swab assays. Six of them were said to have failed azithromycin treatment, though the authors didn't define treatment failure. Six of the patients who had fever and received doxycycline or levofloxacin became afebrile within 24-48 hours. Needless to say, this doesn't translate to great evidence that macrolide resistance is clinically important; it does point to the fact that we need randomized controlled trials to answer this question. Unfortunately, studies need funding, and this condition isn't likely to be profitable enough for funding from a pharmaceutical company. My only takeaway from the study is that further evaluation and treatment should be considered in children with possible pneumonia in whom symptoms worsen or fever persists more than a few days. Unfortunately, M. pneumoniae susceptibility testing isn't routinely available. For mild community-acquired pneumonia in children, amoxicillin is the treatment of choice, with azithromycin as a second-line agent. Switching to doxycycline or levofloxacin should be reserved for macrolide treatment failure, however that is defined.

Certainly we are having a banner year for mycooplasma respiratory infections, likely a combination of the normal mycoplasma surges we see every few years and lack of exposure during pandemic years. Which brings us to ...

Immune Debt

I really liked this new article that looked at the concept of a dose response effect in immune debt, i.e. that the magnitude of illness we see in rebounds of respiratory infections post-pandemic should be proportional to how much less frequent these infections were during the pandemic. The statistical methods in the study are somewhat beyond my expertise, but I mostly think the authors proved their point that lifting of non-pharmaceutical interventions (NPI) around the world seemed to be a point of increase for various respiratory infections. Here's a sample of the findings.

If this is all true, presumably we'll be back to the "old normal" of seasonal respiratory infections soon (barring another serious pandemic).

UTI Diagnosis

I must confesse my eyes rolled when I saw the title of this new study. Early in my career I was involved in UTI research. I've been very disappointed in analyses of UTI diagnosis in recent years because most of them seemed to ignore how variable accuracy of different UTI diagnostic laboratory methods are, even for something as basic as urinalysis. For example, it makes a big difference whether the number of white blood cells in urine is determined by machine (usually flow cytometry), manual counting by a lab technician with or without use of a hemocytometer, or just a urine leukocyte esterase dipstick. So, I was very pleasantly surprised that this group of investigators highlighted precisely those concerns. This was a study of around 4000 febrile children evaluated for UTI with urinalysis and culture, and the results showed that virtually all urinalysis components were poor at predicting a positive urine culture, defined as > 50,000 cfu/mL of a single pathogen in a catheterized urine specimen. The authors concluded that around 20% of children with febrile UTI could have normal urinalyses but also acknowledged how difficult it is to factor in asymptomatic bacteriuria (estimated rate 2%, but tough to assign an exact number) and specimen contamination. I don't think this study solves any of these issues, but it is an important contribution to our understanding of UTI diagnosis.

WRIS and Nowcasting

Last week CDC published a more detailed explanation of how the time-varying estimated reproductive number (Rt) can be used as an early warning for changes in respiratory pathogen transmission activity. This report is of interest mostly to true epidemiologic nerds, so of course I found it very enlightening. The authors did provide convincing evidence that this methodology has been working well recently.

We're not due for another respiratory illness outlook update from the CDC until mid-December, they only provide these every 2 months, but we remain mostly quiet. I suspect we'll see RSV and influenza hit pretty soon around the country. Again, you can check your own local illness and wastewater activity at the CDC' site.

Beware Studies Based on Administrative Data

This is one of my pet peeves: not the studies themselves, but how too much importance seems to be given to them in the lay press (bolstered by academic organizations seeking to get their names in the news). A new study shows how variable results can be from these databases, using the example of invasive bacterial infections in febrile infants. It's easy to imagine how any system based on diagnosis codes entered into various databases could lead to classification errors, but this report provides an excellent example to keep in mind. Any study using an administrative database should evaluate accuracy of diagnoses on a subset of patients to give some evaluation of the accuracy of their results (IMHO).

New 2025 Vaccination Schedules Published

The information isn't new, just based on prior FDA and ACIP deliberations mostly happening over the summer, but now we have the colorful schedules to use. The AAP has a quick summary of changes.

Happy Thanksgiving!

I have so much to be thankful for this year, and I hope not to repeat the Wiedermann Thanksgiving Massacree of maybe 30 years ago. I won't explain in full; it's too painful to spend anything like the 18 minutes, 34 seconds that Arlo Guthrie took to explain his Alice's Restaurant Thanksgiving Massacree of 1965. (Restaurant namesake Alice Brock died a few days ago.) The short version is that my attempt to create the perfect turkey gravy ended badly in an oil slick of glass shards in the kitchen. Why I'm still allowed to have any Thanksgiving responsibilities at all is a prime example of my wife's incredible powers of forgiveness.

We'll be hosting a relatively small gathering at our place this year. My duties are limited to turkey, gravy, and drinks. Starting today I'll have my checklists made out, separated into daily tasks. Thursday itself will have a well-choreographed timeline to include oven and stove use times in our smallish kitchen. As I said at the start, these scraps of paper will bear little resemblance to how the meal actually unfolds.

I won't go into detail about all the food-borne illnesses linked to turkey dinners, but please make good use of your food thermometer and follow guidelines.

And, speaking of Arlo, some of you might be interested in his live recording of "Amazing Grace" with Pete Seeger in 1993 (around the time of the Wiedermann Massacree!). It's 13 minutes of music and meanderings still meaningful in today's world.

Summer Sleuthing 2

Bud WiedermannAugust 11, 2024August 11, 20242 Comments

Last week I mentioned I'd make a poor politician or salesman. I didn't mention other professions, but I wonder if I might have been a successful detective. I had a consult last week that took all of my sleuthing skills, a newborn exposed to maternal syphilis that required me to track down mother's history dating back to 2017 as well as a sibling who turned out to have been a patient of mine a few years ago - not the type of continuity of care I'm looking for. This newborn, like the sibling, will need IV penicillin treatment but most likely will be fine in the long run. The entire consult took me about 2 hours compared to my usual 1 hour. That's why pediatric ID docs are at the bottom end of physician reimbursement but also why I love the profession.

I've been involved in some other detective work recently, but first a review of what's bubbling up as summer is winding down.

More Oropouche Concerns

This is a stark example of today's world - no matter where an infectious disease outbreak occurs, it can affect all of us. The European Centre for Disease Prevention and Control has issued a travel alert for countries in Central and South America experiencing epidemic Oropouche virus disease. The EUCPC found 19 cases of Oropouche disease in European Union residents this year, all linked to travel to Cuba or Brazil. No such alert has been issued by the US CDC, but US citizens should take note.

Summer travel planning should include assessment of disease and other safety risks in foreign countries.

Mpox Redux

I had hoped mpox had settled into a mostly endemic situation in the US, which is in itself a defeat of sorts, but new concerns have arisen from the outbreak in the Democratic Republic of the Congo that could extend to the US. The CDC's Health Alert Network has issued a new alert as cases spill over from the DRC to neighboring Burundi, Rwanda, and Uganda. The clade involved, clade I, is more transmissible and perhaps has a higher mortality than the more common clade II. Risk of exportation to the US is still considered low due to infrequency of commercial air flights from these countries. The alert contains details for case management. Remember, at risk individuals (see below) should receive 2 doses of mpox vaccine.

Persons at risk:

Gay, bisexual, and other men who have sex with men, transgender or nonbinary people who in the past 6 months have had one of the following:
- A new diagnosis of ≥1 sexually transmitted disease
- More than one sex partner
- Sex at a commercial sex venue
- Sex in association with a large public event in a geographic area where mpox transmission is occurring
Sexual partners of persons with the risks described in above
Persons who anticipate experiencing any of the above

Benefits of Vaccination

Speaking of vaccinations and CDC, the latest MMWR included an article estimating benefits, both economic and clinical, of childhood vaccinations over the period 1994-2023. One always needs to be wary of this type of modeling which by its very nature requires analysis of large administrative databases that can have some errors. However, the study authors were very careful and listed 4 study limitations.

First, the analysis didn't include influenza, covid, or RSV vaccination; we can all agree that would result in an underestimation of benefits. They also felt that the recorded immunization rates could be an underestimate, which in turn would underestimate costs of the programs. Similarly, the cost estimates didn't include federal, state, or local program management costs or excise taxes. Their fourth limitation point was that they were unable to consider contributions of other factors like hygiene or social distancing which could have lowered disease rates independently of vaccines. So, of the 4 limitations, 3 could result in overstatement of vaccine benefit. With those caveats, here are their numbers:

That's over a million deaths prevented and over 2 trillion dollars in societal savings.

Sniffles Status

We're still talking covid here, with flu and RSV almost nonexistent. Here's the latest ED visit numbers from CDC.

I was hoping covid wastewater would start to level off, but it is rising in all parts of the US (same link as above).

So, expect more covid in the coming weeks. For now, it seems we are stuck with both summer/early fall and winter covid surges.

Hieronymus Bosch

Not the painter but rather the seriously flawed detective character created by Michael Connelly. Probably the same fondness I have for the detective-like nature of pediatric infectious diseases practice also draws me to (mostly) noir detective literature. This summer I decided to look into somewhat more recent (compared to 1920s-1950s) detective series. Colin Dexter's first book in the Inspector Morse series, Last Bus to Woodstock (1975) was enjoyable, and I'll probably continue to the next installment. Now I've started the first book in the Harry Bosch series, Black Echo (1992). Both books are littered with beautiful writing, such as this musing by Bosch: "The sky was the color of bleached jeans and the air was invisible and clean and smelled like fresh green peppers."

I thought about that line as I was outside in the garden trying to figure out what species of butterfly was sampling the Joe-Pye-weed. I have a love of butterflies dating back to my childhood in south Texas, though I've forgotten almost everything I've learned from that time. We don't have nearly as many butterfly species in Maryland as in my home town, but it's still fun to watch and study them. This one black butterfly has been hanging around for several days; in fact, it's right outside my window now. Unfortunately I can't decide if it is the somewhat more common black swallowtail (Papilio polyxenes) or the rarer spicebush swallowtail (Papilio troilus). Real butterflies often don't look exactly like their pictures in reference materials. After several days and about 15 photos of different aspects of the wings and thorax, I decided to surrender and ask BAMONA (Butterflies and Moths of North America). I've submitted photos, dates, locations, and behavior details and now waiting on a reply from an expert. I'll let you know if they reply.

STOP THE PRESSES: BAMONA just sent me a reply, moments after my initial posting. It is a "dark-form female P. glaucus." For the uninitiated, this is the tiger swallowtail, but the picture below looks nothing like the typical tiger swallowtail. Also amazing, my iPhone identified the photo as P. glaucus, which I laughed as being another failure of artificial intelligence. You can bet I'll be reading more about this dark form butterfly.

Coming Up For Air

Bud WiedermannJune 20, 2021Leave a comment

Well, vaccines are starting to turn the tide and even the cicadas are retreating now. I'm hoping to recommit to Pediatric Infection Connection this summer and try to post weekly commentary that will be at bit more concise than my traditional rambling style. I will try to limit myself to just 2 topics a week, but starting off I'm already breaking that pledge with 3 topics.

1. A Conflict of Interest

For the first time in maybe a couple decades, I need to declare a conflict of interest up front. I am overseeing the Pfizer COVID-19 vaccine trial at Children's National Hospital for children 6 months through 11 years of age. While I don't think this will color any of my commentary here, implicit bias has been recognized as a confounder in scientific and Evidence Based Medicine circles for many years. I will do my best to recognize that and be objective.

2. Keeping Straight with SARS-CoV-2 Variants

In case you hadn't noticed, the terminology for variants has changed yet again, I think for the better but also adding to the public confusion. The purpose is laudable: eliminating the possibly pejorative naming of variants by site of first detection and also doing away with confusing codes. I'm very much in favor of getting rid of the geographic references to outbreak agents. Some of you know that the 1918 H1N1 influenza A pandemic was also known as the Spanish Flu, but in fact the evidence would suggest that a better name is the Kansas flu. Such nomenclature opens the door to discriminatory practices.

Now we are just using Greek letters for SARS-CoV-2 variants, though I fear we will run out very soon! The CDC has a summary of these.

I want to focus on the delta variant which has been the focus of much attention in the lay press. This variant is officially a "variant of concern" and is very much worthy of concern. I don't think it is oversimplifying to focus principally on 3 features of variants. First is transmissibility, or how easily the variant can spread in a population. As the pandemic has evolved, probably the most accurate early sign of transmissibility is how quickly a new strain becomes predominant in a population. The delta variant is striking in its spread, now the most common variant in the UK and soon to achieve that status in the US. It is clearly more contagious than the original strain and early variants.

The second feature is virulence, or whether the variant causes higher rates of severe disease and death. In my opinion, the jury is still out on this for the delta variant. Certainly we have seen appalling severity of disease with this variant in India, but I cannot sort out from the reports how much of this could be due to properties of the virus itself versus healthcare access and other issues.

The third, and perhaps most fearsome to those residing in highly-vaccinated communities, is whether the variant is able to evade host immunity and cause a higher rate of infection in those who have immunity from either natural infection from another SARS-CoV-2 strain or from immunization. In this regard, the delta variant clearly can evade immunity to some extent. Thankfully full vaccination seems to protect from severe disease, but partial vaccination is much less effective. It really causes concern for all those people who skipped the second dose of the Pfizer or Moderna vaccines.

Also remember that every person who is infected with SARS-CoV-2 represents a new opportunity for new variants to appear.

Myocarditis and COVID-19 Vaccines

We must be certain that these new vaccines are safe, and in particular that the risk/benefit ratio is favorable. This is especially important for children where, although severe COVID-19 and MIS-C cases occur, the rates are much lower for complications than for adults.

The CDC had planned an update on myocarditis cases associated with COVID-19 disease for June 18, but this was postponed for a week due to the new Juneteenth national holiday. Now it is to be incorporated into the regular meeting of the ACIP scheduled for June 23-25.

However, based on the data that have been released so far, it does seem increasingly plausible that one or more of the COVID-19 vaccines can cause myocarditis. They are still so rare that it is difficult to be certain that it is happening above the expected rate of myocarditis from other causes in the population. It is unlikely to be anywhere near as common as the rates of myocarditis from natural SARS-CoV-2 infection and thus at this time suggests a clear benefit from vaccination. If you're interested, check out a nice study of COVID-19 myocarditis in Big 10 conference athletes.

Stay safe and enjoy the summer!

COVID-19 TW3, September 27-October 3, 2020

Bud WiedermannOctober 4, 2020Leave a comment

I'd be surprised if any of this blog's readers would catch the reference to TW3, an abbreviation for a short-lived television series, That Was The Week That Was, first appearing in England on the BBC and then in the US. It was a bit of a parody of current events, and I'm not even sure how I still remember it except for the fact that its writing crew included one of my favorite children's book authors, Roald Dahl, as well as a couple of future members of the Monty Python comedy group. That obtuse reference aside, this past Thursday I was planning to post a list of 3 new items of interest regarding our current pandemic; then, our President developed COVID-19 disease.

At this point we should all be pleased that he appears to be stable, but I wish we had more details of how contact tracing and quarantining is going related to all the possible contacts. By now (Sunday October 4) all contacts should have been notified and plans for testing, quarantine, and/or isolation should be complete. Regardless, those original 3 items are still worthy of mention.

The Children's National Hospital-National Institute of Allergy and Infectious Diseases 3rd Annual Symposium. This event was held on September 29 and initially was established to build on collaboration in research and education between CNH and NIAID. This year the symposium focused on COVID-19 with quite a lineup of speakers, including Dr. Anthony Fauci from NIAID, Dr. Peter Hotez from Baylor College of Medicine (and formerly from GWU), and Dr. Ezekiel Emmanuel from U. Pennsylvania. The presentations were a mix of more general and/or clinical presentations along with basic science updates, particularly in immunology. Anyone can access the entire day's session at a CNH link. I highly recommend the above 3 speakers and also the question and answer periods between the different sessions.

National Academy of Science, Engineering, and Medicine Framework for Equitable Allocation of COVID-19 Vaccine. On October 2 NASEM held a webinar discussing their 237-page report, long awaited by many of us who have been following the progress of this very important advisory committee. Anyone can download a digital copy of the report at no cost. The committee was co-chaired by Dr. William Foege, a former director of the CDC, and Dr. Helene Gayle, who has held many key international healthcare positions including heading the Bill and Melinda Gates Foundation and then CARE. (I might add she is a graduate of CNH's pediatric residency, though before my time there.)

I was very impressed by the thoughtfulness, breadth, and depth that went into the report. This group actually completed the entire plan in about 2 months, an amazing feat. Of course the report is a lot to get through, but if you want to browse look at page 86 of the PDF document about the allocation framework, the Table on page 90, the discussion beginning on page 92, and the graphic below from page 94. The exact plans for implementation will depend primarily on the Advisory Council for Immunization Practices, NIH, and other agencies and when/if various vaccines are approved. Clearly it will be a very complex undertaking, but I am very much in agreement with the group's foundational principles and plan. I hope to have time to describe the plan in slightly more detail at the next Montgomery County Pediatric Society meeting on October 12.

"The Carnage of Substandard Research During the COVID-19 Pandemic." This is a direct quote from the title of an article published in BMJ last week, quite an eye-catcher! Despite the sensational title, it's an excellent discussion of the difficulties of interpreting medical research and reports in the pandemic era, although all of these problems existed previously. The author is a bioethicist, and she highlights some key issues including the number of retractions or withdrawals of articles, the large number of studies published only on pre-print websites that do not undergo peer review, and the overall substandard research methods, perhaps fueled by the urgency of the pandemic but resulting in hasty conclusions. It's a short article, take time to read it and decide where you stand.

Tag: vaccination