July 2025 – Pediatric Infection Connection

Royalty in Our House 2

Bud WiedermannJuly 27, 2025July 27, 20252 Comments

Our dog Abby had a surgical procedure this week and is supposed to be confined to an "Elizabethan collar," better known as a "cone of shame." Because she refuses to do anything while wearing it we've been leaving it off when we can observe her closely, resulting in just one unauthorized bandage removal so far.

I note in passing that ACIP/CDC must have heard my recent grumblings; they posted the recordings from last month's crazy meeting. I still haven't gotten up my resolve to look at it yet - too painful. The next meeting is planned for August/September, but no date or agenda yet.

Meanwhile....

RSV

No, the season hasn't started yet, but a couple of articles caught my eye.

First, investigators from CDC and other institutions looked at 2022-23 data from the RSV Hospitalization Surveillance Network to better understand risks for RSV hospitalization of infants. A variety of underlying medical conditions were important for older infants and children, compared to the birth - 2 month age range.

These "UMCs" also figured prominently in ICU admissions:

Importantly, children without UMCs comprised a large proportion of children in their second year of life hospitalized for RSV:

Which all segues into another report, already highlighted in recent ACIP meetings so not really new data, confirming that nirsevimab, the long-acting monoclonal antibody protecting from RSV, works really well.

Some of you may recall this was a study of over 30,000 healthy term infants receiving care from Kaiser Permanente Northern California during the 2023-24 season. Please be prepared to offer RSV monoclonal antibody to infants born to mothers who did not receive RSV vaccine during pregnancy. Information is readily available though not yet updated for the recent clesrovimab approval.

Pediatric Flu Mortality

Numbers continue to trickle in for our most recent flu season, now at 266 pediatric deaths.

Pediatric influenza mortality is defined as a death in child less than 18 years of age with a compatible clinical illness and positive influenza test, where there was no complete recovery from the time of acute illness until death. This past year, 43.6% of children dying from influenza had no underlying high risk condition. Of the children who were eligible for flu vaccination and their status was known, 90% were not completely immunized against flu. Based on the reporting methodology, we don't have a control group to directly compare with the 90% number, but it still suggests we could prevent the vast majority of flu deaths in the US with better immunization coverage.

ITP Recurrence With 2nd MMR Vaccination

Those busy folks at Kaiser Permanente Northern California published a new study looking at risk of immune thrombocytopenic purpura recurrence following a second dose of a measles-containing vaccine in children. The population included 960,000 (!) children receiving 2 doses of MCV in their care system.

Within 6 weeks after the first dose of MCV vaccine, the rate of confirmed ITP was 5.4/100,000 children (95% CI 3.94-6.89) and numbered 52 children total. After a second dose of MCV, the rate was 1.0 per 100,000 (0.56-1.91) among children who did not have ITP after the first dose. None of the 52 children with MCV-associated ITP with the first dose had ITP following the second dose. Given the small numbers of ITP cases, this study cannot exclude a risk for recurrence as high as 7%. So, it should be reassuring to parents of children experiencing MCV-associated ITP that a second dose is safe.

COVID?

I remain at a loss to know how to predict when our next covid surge will be, but it may be worth looking at 2 early warning indicators to get perspective. Percentage of ED visits for covid are creeping up but still very low and look nothing like past years so far.

The most recent covid test positivity rate is 4.2%.

The problem with our current information, as I've stated before, is that rates of test-seeking behavior are much different in our current climate compared to pandemic years with easier access to testing. I suspect we will see a surge sometime - too many unvaccinated individuals coupled with seemingly lower infection rates in the past year or so would portend a large population with waning immunity to SARS-CoV-2.

My Dog Doesn't Look Like Queen Elizabeth

I'm not sure what her majesty, the last of the Tudor dynasty, would think of her image being appropriated for canine apparel. And, that's an ermine in the portrait, Mustela erminea, far removed from our Canis lupus familiaris.

Rain, Rain, Go Away

Bud WiedermannJuly 20, 2025July 20, 2025Leave a comment

Apparently the English version of this nursery rhyme dates to 1659, a little before my time.

Our rain gauge totaled 4" this morning, after an intense 2 hours of rain last night. The local forecasts hadn't predicted this, so I decide to consult my 2025 Old Farmer's Almanac, sort of a ouija board of weather and other cosmic events. I wasn't surprised to see that their July weather forecast for my area was off a bit: average precipitation for the month, with July 18-22 listed as sunny, then heavy rains north (Maryland is at the southern end of their Atlantic Corridor). Of course I found a rabbit hole to fall into while I was thumbing through the book.

Otherwise it's a quiet summer.

Success in Senegal

The World Health Organization announced that Senegal has joined a growing list of countries that have eliminated trachoma, the leading infectious cause of blindness worldwide. Private donations of azithromycin from Pfizer greatly contributed to this success. Senegal is the 25th previously endemic country to eliminate trachoma, but 32 countries remain at risk. Most (90%) of the estimated 103 million at risk people reside in Africa.

COVID Still Low

I felt obliged to mention this given that some news media have breathlessly reported an uptick in covid. Let this serve as a reminder that an uptick from one low level to another low level does not a surge make.

The CDC's Modeling and Forecasting page explains this very well. They use a calculation based on a time-varying reproductive number abbreviated R_t. "While R_t tells us if the number of infections is likely growing or declining, it does not reflect the burden of disease." [Bolding is mine.] Here's the map as of July 8:

I also clicked on Maryland to get the inserted table and the graph below. As stated in the Table, even though Maryland is likely growing, the percentage of ED visits for covid were still very low.

Covid seasonality hasn't yet declared itself, now over 5 years since the pandemic started.

Covid Planning in the UK

Speaking of seasonality, the UK hammered home this point in their new covid vaccination recommendations for 2026-2027. (They are really planning in advance!) Even I wouldn't qualify to receive covid vaccine in the UK that year. It's important to note that, as I've said in the past, these recommendations are based purely on cost effectiveness, not on whether there is any net benefit from vaccination for individuals. Unfortunately, with fewer data (fewer resources to track infections, fewer people being vaccinated, fewer people hospitalized, etc.) to guide these studies, the UK still uses a cost-effectiveness study with data from March 2023 - March 2024 to make their estimates. US data from that time period suggest net benefit from covid vaccination at all age groups; the difference in approach is based on the cost to prevent 1 bad outcome from covid infection - it's becoming more and more expensive.

That said, the UK recommendations for 2026-7 are to provide covid vaccination to all adults 75 years and older, residents in a care home for older adults, and immunocompromised people ages 6 months and older.

With regard to seasonality, here is what the UK says about it: "There continues to be no evidence of seasonality in COVID-19 epidemiology."

General Vaccine News

I wanted to highlight a couple new studies, both moderately enlightening though not likely to budge the entrenched anti-vaccination groups. The first study is a Danish national cohort study looking at cumulative aluminum exposure from vaccines and chronic health issues. Aluminum has been used for decades as an adjuvant in many nonlive vaccines. As befitting a setting with a robust national health service, investigators were able to follow about 1.2 million children born in Denmark between 1997 and 2018 and residing in Denmark at least to age 2 years. They looked for evidence of 50 chronic disorders in the national database, though they did not look at individual medical records.

Injection of high doses of aluminum into rats showed neurotoxicity, and studies in humans with very high exposure (dialysis, occupational inhalation, IV via parenteral nutrition) also have suggested harm. A much smaller US study looking at aluminum in vaccines and various outcomes did suggest an association with asthma.

The amount of aluminum exposure for the Danish cohort children was in the few mg range.

Adjusted hazard ratios did not suggest any increase risk of chronic conditions; in some instances a decreased risk was seen.

The study is very reassuring, but I doubt it will have much effect on vaccine hesitancy trends.

The second study I wanted to mention is nothing new, but it is a timely and excellent review of the complexity of issues the test-negative study design (TND) often used by CDC and others to measure vaccine effectiveness. A couple members of the new ACIP group talked around this during last month's meeting but didn't really provide specifics. The 2 authors of the review article are from the University of Hong Kong, far removed from CDC, although 1 author has consulted for multiple vaccine companies.

I liked their representation of TND study steps:

Without getting too bogged down in details, the slippery banana peel in TND studies is that people have different behaviors with regard to when they seek medical attention and whether they choose to be vaccinated, and this variation must be taken into account. Depending on how a clinical case is defined for a given study, the VE can vary widely, probably based on how well the definition provides correction for these varying behaviors. TND studies, though expensive, require fewer resources to carry out compared with prospective cohort or case-control studies. The latter study designs are likely to be less prone to some of the error in VE estimates inherent with TND.

At the moment we are in a particular conundrum with planning better VE studies. Grant funding and human resources at the federal level are now greatly reduced. We are left with an easy avenue for anti-vaccination groups to criticize TND studies coupled with greater barriers to carrying out trials utilizing alternative methodology.

Tuskegee Study: Should Unethical Research Publications Be Retracted?

The Tuskegee Study, started before the penicillin era but then denying access to penicillin to enrollees later, is perhaps the darkest hour of medical ethics in US medical research history. We are in an era of relatively high rates of retractions of scientific publications, mostly related to altered or imprecise data. This new report discusses and offers advice to journals about what to do with published studies later declared to be unethical. It's the best summary I've seen of all the Tuskegee publications, covering 1936 - 1973. The study wasn't stopped until 1972, still hard for me to comprehend.

The study's authors suggest that journals adopt clear policies for dealing with unethical research publications, not a very controversial viewpoint but certainly overdue. A problem remains in that most older studies would violate current ethical standards that we now consider routine, such as informed consent. The concept of informed consent first appeared in the US in the early 20th century in a few court cases, but it wasn't until the Nuremberg trials following World War II and other legal cases in the US in the late 1950s that the concept became more imbedded in US human research. See this article for a historical overview.

Wow Your Friends at Cocktail Parties

Well, perhaps not, but I still couldn't resist this new formula for determining the day of the week for any date starting with the year 1753. It's very simple arithmetic, just adding up the last 2 digits of the year + one-quarter of those 2 digits (discard any remainder) + given day of the month + the Key Number for the month. Take that sum and divide by 7; the remainder of that division codes to the day of the week with Sunday being 1, Monday 2, all the way to Saturday which is 0.

Unfortunately it's really not that simple and involves knowing those Key Numbers for each month that follow no pattern (January is 1 but 0 in a leap year, September is 6, October is 1, etc.) and different correction factors for weekdays before 1900 and before 1800, plus another correction for 2000-2099.

So, you can ask me at our next social gathering to calculate the day of the week for your birthdate, but I'll only be able to answer you if I've saved the link to an automated spreadsheet like this.

Have a nice (dry) week.

It’s Not the Heat, It’s the Humidity

Bud WiedermannJuly 13, 2025July 13, 2025Leave a comment

I just watched a gentleman, probably close to my age, jog by my house. Current temperature is what should be a comfortable 79 degrees, but with humidity 87% the "feels like" temperature on my phone app is 82 and my real world experience walking the dog this morning I give a 4 on my 5-point uff da scale,* where 5 is completely miserable.

It's also been pretty steamy in the healthcare policy arena this past week. A group of medical and public health societies and an unnamed individual have filed a lawsuit against our HHS Secretary, FDA Commissioner, NIH Director, and CDC Acting Director seeking to overturn withdrawal of recommendations for covid vaccines. At about the same time, the HHS Secretary cancelled last week's meeting of the United States Preventive Services Task Force, a terrific group of 16 highly qualified medical and public health experts serving on a rotating voluntary basis under the auspices of the Agency for Healthcare Research and Policy. They publish recommendations for a variety of medical conditions; current work in progress includes statements on interventions for tobacco cessation in adults and vision screening in children ages 6 months to 5 years. So far in 2025 they had published 5 recommendation statements, including one for syphilis screening in pregnancy. The recommendations can in part determine insurance coverage for various tests and treatments. In general, the evidence bar to clear the USPSTF is pretty high; much of the time their recommendations serve to point out deficiencies in our knowledge base and provide direction for future study. Of course I'm wondering if USPSTF is headed for the same downhill trajectory we saw with ACIP - cancelled meetings followed by firing of experts who are then replaced with pseudo-scientists with an ax to grind.

Thankfully I found many intriguing topics to discuss this week. I picked a few.

High Consequence Infectious Diseases

This is an official designation in the UK, and I was interested to see a recent breakdown, especially noting infections that didn't qualify for HCID status. HCID definition includes an acute infectious disease that typically has a high case-fatality rate and may not have effective prophylaxis or treatment. HCID often are difficult to recognize and detect rapidly, have an ability to spread in the community and within healthcare settings, and require an enhanced individual, population and system response to ensure effective management. They are organized by mode of transmission as follows:

Contact HCIDs

Argentine haemorrhagic fever (Junin virus)
Bolivian haemorrhagic fever (Machupo virus)
Crimean Congo haemorrhagic fever (CCHF)
Ebola virus disease (EVD)
Lassa fever
Lujo virus disease
Marburg virus disease (MARD)
severe fever with thrombocytopaenia syndrome (SFTS)

Airborne HCIDs

Andes virus infection (hantavirus)
avian influenza A(H7N9) and A(H5N1)
avian influenza A(H5N6) and A(H7N7) [H5N6 has not yet been reported to have human-to-human transmission]
Middle East respiratory syndrome (MERS)
Nipah virus infection
pneumonic plague (Yersinia pestis)
severe acute respiratory syndrome (SARS) [this is the original SARS from the early 2000's, no known cases since 2004]

Looking at the HCID definition, I think it's clear why SARS-CoV-2 wasn't on the list - we now have effective diagnostic tests, preventive measures, and treatments available. I was a little surprised not to see mpox in the list of contact HCIDs. The supporting evidence stated that mpox was "derogated" by the UK Advisory Committee on Dangerous Pathogens. Yes, I admit I had to look up the definition of derogation; it indicates an exemption or relaxation of a rule. Both COVID-19 and mpox are still significant threats to global health, but for UK purposes not having them on the HCID list means that they can be managed outside of designated HCID treatment centers.

Chagas Disease in Florida Kissing Bugs

Not a huge surprise, but now we have evidence of significant colonization of Florida triatomine bugs with Trypanosoma cruzi, the parasite that causes Chagas Disease. Various investigators and community programs collected 310 Triatoma sanguisuma bugs from 23 counties (mostly northern and central Florida) over the period 2013 - 2023. About 35% of the bugs were found in human dwellings, so this isn't just a phenomenon taking place in Florida wilderness. About 30% of the insects carried T. cruzi. The investigators also analyzed the blood sources. Mammals comprised 60% of the sources, ectothermic vertebrates (amphibians and reptiles) 37%, and cockroaches 2.5%. Importantly, humans represented 23% of the infected blood meals.

Just in case you have a Florida trip upcoming, here's the distribution though note that not all geographic areas of the state were sampled.

Probably more importantly, here's what the bugs look like. At left is an adult female and on the right are nymphal stages. The bars represent 2 mm for each photo.

Triatomes commonly are referred to as kissing bugs because they like to bite us on the face. Kissing bugs can be found in most US states, generally sparing the northernmost states.

Association of First Trimester UTI with Congenital Malformations

I was surprised I didn't see anything about this in the lay press, maybe I'm not watching enough TV. Previous studies have variously suggested an association with first trimester exposure of pregnant people to trimethoprim-sulfamethoxazole (TMP/SMX) or nitrofurantoin and subsequent congenital malformations in their newborn infants. Investigators from multiple institutions now have published a cohort study of around 70,000 pregnancies identified through a commercial insurance database to have received either TMP/SMX, nitrofurantoin, a fluoroquinolone (ciprofloxacin, levofloxacin, or ofloxacin), or a beta-lactam antibiotic to treat a UTI during the first trimester of pregnancy in the years 2006 - 2022.

Results suggested a higher risk with TMP/SMX exposure but not with nitrofurantoin for some cardiac defects and for cleft lip and cleft palate, when compared to mothers who received beta-lactam antibiotics for their UTI. Part of the data are shown below.

You can see at the right of the table that the 95% confidence intervals do not cross 1.0 for these 2 circumstances, indicating a statistically significant association. Also note, however, that the total number of events are a relatively small percentage of the total exposures. Still, these malformations carry significant morbidity. The American College of Obstetricians and Gynecologists cautions against use of TMP/SMX and nitrofurantoin in the first trimester of pregnancy. It's easier to understand why TMP/SMX might be able to cause malformations because both components inhibit folate metabolism. This study lends support to avoiding TMP/SMX in this setting.

Some Potpourri

Measles

You've probably seen a lot about US measles cases now surpassing 2019's total, so we now have to go back to 1992 to see a higher number of cases; this occurred while the US was still trying to implement 2nd doses of MMR for the 4 - 6 yo age group. Although new cases are reported every week, it's important to note that things have tapered off a bit, enough for the CDC to go back to just weekly case count reporting.

I'm holding my breath that we won't have another big outbreak somewhere, but MMR vaccine hesitancy is against us.

West Nile Virus Review

A nice one was published in JAMA last week, worth reading for a general refresher. Remember that most infections are asymptomatic. Symptomatic individuals usually experience a self-limited febrile illness, but the real fear is neuroinvasive disease.

The live link to the testing algorithm is here.

*Uff Da

Those who know me personally might wonder why I would appropriate a Norwegian term since my ancestry is most certainly not Scandinavian. I think I can claim some rights to the term. My long-suffering wife was born in Minnesota, and both sides of her family have Scandinavian roots. Furthermore, my mother was born and grew up in the Upper Peninsula of Michigan, a hotbed of former Scandinavian residents.

I survived several (6-month-long) summers in Houston, a hotbed of humidity, but I never became accustomed to it.

Looking forward to September.

Never Give Roses in Even Numbers

Bud WiedermannJuly 6, 2025July 6, 2025Leave a comment

I've just returned from our family's annual beach vacation, quite an evolution over a few decades. Now it's tough to find a time when all 3 sons and families can gather at once, and last week had some staggered arrivals. I also noted some major role reversals. Now all 3 sons and spouses/significant others spent some part of the week attending work meetings and putting out various minor fires at their respective institutions. I, on the other hand, attended no meetings and spoke to no work colleagues, though of course I still had to read through all my pediatric infectious diseases feeds. I had even more time for book reads, from which today's title emerged.

I confess I took a little time to do some background research on new ACIP committee members, something I purposely avoided before last month's meeting. Without dwelling on this, I did find most members espousing viewpoints in the past that clearly fall heavily in the anti-vaccination camp and explain a lot of what happened at the meeting.

I found a few interesting articles from last week that I wanted to share with you.

Flu Vaccination During Pregnancy

Researchers from Kaiser Permanente Northern California carried out a cohort study to look at how influenza vaccination of pregnant people impacted newborn influenza infection. Because it is a large healthcare system with most care given within KPNC, this is the closest thing we have in the US to a national health system that can limit the amount of error introduced in studies where most US residents are likely to seek healthcare in many different health systems.

The pregnant participants consisted of people 15 - 45 years of age who were enrolled at KPNC long enough to have their vaccine and care status known and for infant follow-up. The study enrolled from January 1, 2011, to December 31, 2022. The results below show vaccine effectiveness against PCR-confirmed influenza infection in their infants, which was quite good though clearly waned after 4 months of age.

I was surprised to see that overall flu vaccination rates were somewhat poor at KPNC, which has good vaccine reminders in their EMR. The investigators also looked at infant influenza hospitalization rates: 9 infants (0.1%) in the vaccine group versus 20 (0.2%) in the non-vaccine group, not statistically significant. (A less scrupulous journal or group of investigators could trumpet a 50% lowering of hospitalization in the vaccinated infants to make it sound better, an example of how percentages can be more misleading than absolute numbers.)

Pediatric Covid Hospitalization and Severe Disease Risks

Researchers from several organizations studied the CDC's COVID-NET system to give us a great look at pediatric covid risks from October 2022- April 2024, i.e. a good picture of what to expect in the omicron era where most everyone has pre-existing antibody from prior infection and/or vaccination. It was a fairly labor-intensive undertaking because it involved chart review to determine, as best as possible, that the reason for hospitalization was SARS-CoV-2 infection rather than hospitalization for another illness in a child who just happened to test positive for covid. They ended up with about 2500 cases.

Note that COVID-NET is a database containing information just on hospitalized patients. It covers about 10% of the US population - 90 counties scattered over 12 states. The study has a wealth of data; I'll try to focus on just a couple things.

As you can see below, even in the older age groups hospitalization occurred in significant numbers of healthy children. Weighted rates attempt to account for probability of case selection.

Here's a breakdown of risk factors by age group.

Less than 5% of children were up to date on covid vaccination, though that rate might be falsely low due to vaccine status not recorded accurately in the various databases they used to determine this. Breaking vaccine status down further, about 14% had no covid vaccination in the 12 months prior to testing positive for SARS-CoV-2. 10.3% had been vaccinated during that 12-month period but were not up to date. This report reminds us that, when talking about vaccination risks and benefits, it's important to compare this to the alternative, i.e. being infected and the various risks (hospitalization, long covid, etc.) associated with infection.

Forecasting Follies

Usually I try to avoid reporting on "crystal ball" studies that try to predict the future for various infections - too many variables and assumptions cloud the analysis, plus the mathematical modeling usually is beyond my expertise. Two studies in the past week forced me to reign in my skepticism. Both were carefully performed and have short time frames so that perhaps in a few years I can remember to report back on how well they did.

First is a model to predict mortality increases related to defunding USAID programs. Here's a breakdown of rate ratios for different infections (see comparison to injuries at the bottom) categorized by degree of country dependence on USAID programs.

And the country map showing deaths prevented by USAID programs for the period 2001-2021.

Then we see their forecasted mortality through 2030, assuming funding cuts aren't reversed.

Yes, that's 14 million excess deaths, 4.5 million in children under 5 years of age. I'm hoping cooler heads prevail and USAID support is revived. I don't want to know if these estimates were accurate.

The second report focused on measles. The methodology was a bit different from the study above, but again it's beyond my mathematical understanding and therefore leaves me free to just report on the findings. The investigators compiled the results based on different levels of vaccination coverage in the community - if rates continue to fall, risks of major outbreaks go up. First, they used a basic reproduction number R₀ of 6-10, lower than what is mentioned in various news feeds but probably more accurate for the modern era. From this they derived an effective reproduction number, R_e, that utilizes the truly susceptible population that varies by community vaccination rate.

The current data give a snapshot of 2025 outbreak risk by month.

They then projected their crystal ball to the next 5 years utilizing different rates of decline in measles vaccination rates.

As you can see, if we experience no change in measles vaccination coverage the next 5 years, sadly a very unlikely scenario, we have a little less than 20 states with at least a 10% chance of outbreaks occurring. With a 50% decline, we're up to 50 states.

I hope I'm alive and only semi-senile by 2030 so that I can report back on these measles predictions.

Flowers for Any Occasion

The beach book with the quote in this week's title wasn't my typical mindless beach book except for the fact that it was hard to put down. It required paying attention to details to fully appreciate, and even then I could use another read to get more out of Hernan Diaz's Trust. It was co-awarded the 2023 Pultizer with another terrific book, Demon Copperhead by Barbara Kingsolver. The Diaz book has a very unusual layout, sort of a puzzle to figure out what's real, and I loved it. One of the characters taught me something about flower superstition. "Never gives roses in even numbers .... Even roses are for funerals. Uneven roses are for love." It turns out there are lots of superstitions about numbers of flowers, but I couldn't verify any of them very easily so no links provided.

I can't remember the last time I gave flowers to my long-suffering wife. My lame excuse is that she grows flowers too well for me to make a separate purchase. In the future I'll be closely counting the numbers in any flower vase she puts in front of me.

Month: July 2025