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I regularly read Ron Charles's Washington Post Friday Book Club newsletter, always chock full of interesting topics and writers I haven't yet explored. This Friday he included a quote from controversial (accused of plagiarism) Turkish author and activist Elif Shafak

“... we are living in a world in which there is way too much information, but little knowledge and even less wisdom.… As we scroll up and down, more out of habit than out of anything else, we have no time to process what we see. No time to absorb or reflect or feel. Hyper-information gives us the illusion of knowledge. For true knowledge to be attained we need to slow down. We need cultural spaces, literary festivals, an open and honest intellectual exchange.”

This blog is my attempt to machete a trail through all the various forms of information and provide some bridge to knowledge and wisdom by providing links to reliable original sources. Speaking of which, we are now in the midst of ID Week, probably the most prestigious annual infectious diseases research conference, and many of my regular ID feeds are filled with reports of presentations. However, I virtually never include these reports in this blog, because there is no way via these abstracts to look for potential flaws or limitations in the research, and it is well known that research meeting presentation findings often change dramatically by the time they are published in a peer-reviewed journal, if they are ever published at all.

WRIS

Still pretty quiet on the Winter Respiratory Infection Season, with some hints of beginnings of influenza and RSV increasing. Perhaps the only item of interest is an increase in Mycoplasma pneumoniae activity, probably just a regular wave that tends to happen with this pathogen, though delayed somewhat due to pandemic mitigation strategies. It's not a reportable disease, so it's hard to find good data on incidence over time. As most providers know, this is a self-limited illness that produces generally mild illness (so-called walking pneumonia) and usually not worth diagnosing or treating. Because of its self-limited nature, it's been difficult to demonstrate any benefit of antibiotic treatment compared to placebo, and I doubt we'll see any placebo-controlled randomized trials in the near future.

Compared to last winter, CDC is predicting a 54% chance of a similar combined peak of respiratory illnesses, with a 28% chance of a lower peak and 18% chance of a higher peak.

Infectious Complications of Hurricanes

These tend to get less coverage than do the more obvious loss of life and property destruction occurring immediately during a natural disaster, but the Florida Department of Health is now reporting on a surge in cases of necrotizing fasciitis due to Vibrio vulnificus, a known salt and brackish water pathogen. Here are the numbers:

As a reminder, individuals with immunodeficiencies, but also particularly including chronic liver or renal disease, are at high risk for V. vulnificus complications. CDC has a good summary.

Conjunctivitis

Researchers in Colorado looked at about 200 children with acute conjunctivitis compared to a similar number of children who were either healthy or had URI without conjunctival involvement. Long story short, they found no benefit of ophthalmic ointment treatment, but did see a 20% incidence of antibiotic side effects. The study itself didn't replicate real-world situations for providers; for example, they employed broad spectrum PCR testing looking for a large number of bacteria and viruses. The study doesn't give us much direction for practical approaches to this problem but does serve as a reminder to limit topical and other antibiotic use in acute conjunctivitis in children,

Outpatient Infant Botulism?

I would never have thought of this, I've only been called for hospitalized children with infant botulism. It turns out, though, that there are rare instances of milder disease managed as outpatients. A team reviewing the California Department of Public Health data from 1976 - 2021 found 17 of 4372 cases (0.4%) were outpatients. (Note that California cases account for about 1/3 of all US infant botulism cases.) Here's the breakdown of clinical findings.

The median age at onset of symptoms was 20 weeks, with a range of 6 - 55 weeks. Only 1 child had been exposed to honey.

Polio Updates

The second round of novel oral polio type 2 vaccinations have begun in Gaza, though I haven't heard much about ceasefires to help facilitate this critical second round. Meanwhile, this week the Global Polio Elimination Initiative had to bow to reality and revise plans and timeline for polio elimination worldwide. Now, the end of 2027 is the target for elimination of wild poliovirus infections, with end of 2029 for elimination of type 2 vaccine-derived polio. This will take significantly more funding, and the greater the risk of prolonged or new wars the less likely these targets will be achieved.

The DIKW Pyramid

I'm accustomed to using the evidence-based medicine pyramid for hierarchies of study design in medicine, but in researching Dr. Shafak's quote about wisdom I happened onto the Data, Information, Knowledge, and Wisdom pyramid. It doesn't appear to incorporate anything about the role of false or misleading data, so I'm not sure if it is a helpful model in our era. As artificial intelligence becomes more entrenched (it's impossible to remove that view from Google Chrome!), we need to be even more vigilant about our data sources.

HAL 9000 looks a lot like my doorbell. Yikes!

After one failed retirement attempt, I'm trying again. I just entered a new phase to decrease my coverage of inpatient telemedicine services at regional hospitals and, if demand isn't increasing terribly, I'll phase out completely. In the meantime, I'm revving up for watching the Winter Respiratory Infection Season (WRIS).

WRIS

Nothing strikingly new or concerning on the covid, influenza, and RSV fronts, according to CDC. Respiratory illnesses, wastewater levels, and ED visits are pretty flat or decreasing most places. Florida is starting to show an increase in RSV; typically that region starts sooner than the rest of the country. Of course all viral activity varies geographically, and you can look at your own region with CDC's interactive program at that link.

I admit to having some personal interest in following this closely now. I'm trying to figure out timing of my flu vaccine; as a septuagenerian I may have more rapid waning of immunity after vaccination than do younger generations, plus preliminary data from the Southern Hemisphere suggests a slightly lower flu vaccine effectiveness this year. The key term here is preliminary. These estimates are based on very low sample sizes, and estimates always change once the full season can be evaluated.

Speaking of vaccines, the UK provided a more straightforward guidance for covid vaccination this year. The eligibility groups are pretty limited:

During the 2024 autumn campaign the following groups should be offered a COVID-19 vaccine:

  • all adults aged 65 years and over including individuals aged 64 who will have their 65th birthday before the campaign ends (31st March 2025)
  • residents in a care home for older adults
  • individuals aged 6 months and over who are in a clinical risk group, as defined in tables 3 and 4 of the Green Book chapter 14a

As I've mentioned before, the UK with its National Health Service relies heavily on cost effectiveness analyses, leading to a more restricted target population than in the US.

Two Viruses on the International Scene ...

Marburg Virus in Rwanda

Marburg activity in Rwanda is increasing, and the CDC sent out an advisory last week. Marburg virus is another of the hemorrhagic fever flaviviruses, like Ebola; it has a high fatality rate. As in other hemorrhagic fever virus outbreaks, healthcare workers are at high risk if they are not careful with exposure to blood and body fluids. Most of us remember the spread of Ebola to the US, and already there's been a scare in Hamburg, Germany, but the ill traveler returning from Rwanda tested negative. The name comes from the German city of Marburg which was one of the sites (the others were Frankfurt, Germany, and Belgrade in what is now Serbia) of laboratory outbreaks of the illness in 1967, linked to African green monkeys imported from Uganda. Let's hope efforts to contain the infection are successful, but it's a tough task in low-resource regions.

Perinatal Chikungunya

A new study from Brazil suggests a relatively high rate of transmission of this virus from pregnant people to their newborn infants. The study period covered the years 2016 - 2020. Here's the summary numbers:

Symptoms in infected infants included, in addition to rash and fever, some more severe conditions like DIC, vesiculobullous eruption, seizure and encephalitis, and respiratory failure. It was both a retrospective and prospective case series, and I learned a new term: ambispective!

... But Also Some International Success

The WHO recently declared Brazil has successfully eliminated lymphatic filariasis as a public health problem, a major milestone. The only countries successful previously with filariasis were Malawi and Togo in the WHO African region; Egypt and Yemen in the Eastern Mediterranean region; Bangladesh, Maldives, Sri Lanka, and Thailand in the South-East Asian region; and Cambodia, Cook Islands, Kiribati, Lao People's Democratic Republic, Marshall Islands, Niue, Pilau, Tonga, Vanuatu, Viet Nam, and Wallis and Futuna in the Western Pacific region. Time to dig out that world map!

Filariasis is one of 20 Neglected Tropical Diseases targeted by WHO for improved control by 2030.

Lower Vaccination Rates in US Kindergartners

CDC updated vaccine coverage rates for the 2023-2024 year and, no surprise, it's dropping. The decrease may be driven at least in part by an increase in non-medical exemptions. This news doesn't bode well for future outbreaks of vaccine-preventable diseases, but the clinical impact is largely determined by geographic distributions at the community level. The site has a lot of data, worth some browsing, but here's a quick look at MMR coverage by state for 2023-2024:

Any state that isn't the darkest blue has high risk for outbreaks. Even within the dark blue states any pockets of poor vaccine coverage, such as communities or schools that have high rates of vaccine-averse parents, could see outbreaks.

How's Your Outpatient Antibiotic Prescribing Score?

A cross-sectional database study of about half a million antibiotic subscriptions in 2022 from Tennessee showed some interesting results. The investigators looked at both appropriateness of antibiotic choice and duration of treatment; only 31% of prescriptions were appropriate for both. Here's the quick look at optimal antibiotic choice by disease:

Here's what it looked like for duration of therapy. Standard durations reflect current guidelines, whereas contemporary durations are taken from more recent studies suggesting shorter courses are effective. The number of days in parentheses are the contemporary durations.

Again, another study worthy of browsing if you commonly prescribe antibiotics for these conditions.

November 5 is Fast Approaching

Although I'm trying to wind down my practice, it seems like my to-do list is twice as long now. We're all busy, but please don't forget to vote!

I just returned from a mad dash to Orlando, FL. No, I wasn't paying Mickey and Minnie a visit, just putting in an almost cameo appearance at the American Academy of Pediatrics National Conference and Exhibition. Apparently they were desperate for speakers because they invited me to give a talk about how to approach reading journal articles. A few dozen attendees politely endured my presentation, but I, and I think even most of the attendees, had a fun time. I also got to chat with a few old friends, always nice.

Although the trip was nice, I was most excited about the notice I received from my bird feeder while I was away. More on that later.

Potpourri

I came across a smattering of unrelated items this past week, grouped here.

I think we could all use some good news from the Middle East now. The WHO announced that Jordan has become the first country in the world to be certified to have eliminated autochthonous (locally-acquired) leprosy. That is no mean feat and required tremendous efforts and resources both from the country of Jordan as well as the WHO. It has been over 20 years since they've had an autochthonous case in Jordan.

The CDC has sent out a notice about mpox prevention through their Health Alert Network. It's not new, but worth reviewing to understand risk groups and to remind us to ask about international travel plans of our patients.

I've deliberately avoided commenting on the possible person-to-person spread of influenza A H5N1 in Missouri, but it's been in the lay press. Close contacts of 1 confirmed case had illnesses that could be consistent with this form of bird flu, but we don't have any test results from the contacts. I just mention it to stress that this is an evolving story. It would be a change for this organism if human-to-human transmission is now common.

Vaccine News

A couple intriguing reports last week from the CDC via the weekly MMWR. First are survey results that give us a glimpse at what happened with childhood immunization rates during the pandemic. It should surprise no one that vaccination coverage at 24 months of age declined by a few percentage points from birth year 2018-19 to birth year 2020-2021. For the combined 7-dose series (doesn't include covid vaccination) the rate dropped from 70.1% to 66.9%. This just adds to the possibility for sustained epidemics especially if clusters of poorly immunized children are grouped together. Here's a list of the national data for the 2020-2021 birth year cohort:

The entire table was too large to put in everything here, but Montana had the lowest numbers followed by California at second worst. You can look up your state and region in the article.

The same MMWR also had some new data on covid in children under 6 months of age. It provides compelling rationale for maternal immunization. First, here's what age-associated covid hospitalization rates look like from the surveillance network:

Further data showed that infant hospitalization rates are higher than rates in the elderly (75 years and above). In a subset of 1148 infant records that underwent extensive review, 9 deaths were recorded. Overall 22% of the hospitalizations involved intensive care admissions. Looking just at the 1065 infants for whom maternal vaccination status was available, it appears that maternal vaccination during pregnancy could be an important preventive measure for severe infant covid illness.

Note the careful wording: "No record of maternal vaccination during pregnancy." This points to the fact that these records might have been incomplete or even wrong - the providers may have recorded information incorrectly, or the mother may have been mistaken about vaccination status and timing. I'm still impressed with the information, especially since these numbers are very recent, from the omicron period when virtually every adult had some sort of immunity either via natural infection, vaccination, or both. Maternal covid vaccination is important to protect both the pregnant person, itself a high risk group, as well as the infant who is too young to receive covid vaccine.

A New Antiviral for RSV?

A placebo-controlled, randomized, double-blind trial of a few hundred infants hospitalized for RSV in China suggests that a newer antiviral agent, ziresovir, might be an effective treatment.

The main endpoint is change in the "Wang score" which is a relatively unvalidated scoring scale for assessing RSV severity. You can see the decline in the score is a bit better with the treatment group compared to placebo, but is the change in score clinically important? As a still wet-behind-the-ears ID attending, I witnessed early studies of randomized, double-blind, placebo-controlled trials of aerosolized ribavirin for hospitalized infants with bronchiolitis; my boss, a renowned pediatric infectious diseases physician named Bill Rodriguez, headed up these multi-center studies. I witnessed potential pitfalls in using scoring systems for bronchiolitis, particularly the problem with intra- and inter-rater reliability in assessments: it's hard to be consistent with scoring when the events you're looking at are somewhat subjective. Also, the aerosolized ribavirin left a fine powder on the infants, difficult to disguise even when the nurse tried to remove it before the investigator did the scoring. So, it wasn't perfectly double-blinded, in some cases not blinded at all. At blinding wasn't a problem with ziresovir, which is administered orally. Aerosolized ribavirin did work, but ultimately the costs outweighed the benefits (plus some risk to providers of inhaling the medication if the patient room was not well-ventilated and potential for teratogenicity), so the practice didn't last long.

I'll wait to see more data about this intriguing new agent. In the meantime, remember we have very effective methods of preventing severe RSV disease in infants by either maternal vaccination or administration of long-acting monoclonal antibody (nirsevimab) to infants whose mothers were not immunized.

Crystal Ball Time

What's coming this winter, and how bad will it be? Don't place any big bets on the CDC's latest predictions, they have only low to moderate confidence with their model, but it's by far the best data we have.

Here goes: "CDC expects the upcoming fall and winter respiratory disease season will likely have a similar or lower number of combined peak hospitalizations due to COVID-19, influenza, and RSV compared to last season."

That's good news. The experts were moderately confident of predictions for individual infections, but it's not really possible to anticipate all of the variables that could change the predictions dramatically, such as immunization uptake. Of course, if a new covid variant arises with a very effective immune escape mechanism, no one will be betting and we'll be in for a bad time.

Here's some more tidbits:

For example, if our summer covid activity peaks early (which it seems to be doing), they predict a milder winter season than if covid continues to rise now.

If you're a nerd like me, you can look at their description of how they developed this prediction model.

For the Birds

Getting back to my bird feeder, regular readers will recall my travails discussed in prior posts, including battling squirrel seed raiders. Things have settled down now, and I seldom see new species, but the past 2 days I've had my first sightings of a red-bellied woodpecker. The first thing I noted from my feeder's video (still photo taken below) is that I don't see a prominent red belly.

Other views show the typical zebra-like striping on the wings - why not call it the zebra woodpecker? - and the Cornell app quickly identified its call as the red-bellied variety. As usual, I couldn't help but see what new woodpecker tidbits I could learn from the worlds of literature and music. My childhood and adolescent "career" playing tenor saxophone made me a fan of big band music, particularly of Glenn Miller, and I discovered he had recorded The Woodpecker Song. It's not that great in my opinion, but at least I learned something new. One of my other musical heroes, Chuck Berry, recorded a purely instrumental (with saxophone solo!) song called Woodpecker. My favorite find, though, was a new-to-me poet, Elizabeth Madox Roberts. She was a Kentucky-born daughter of a Confederate soldier, active as a poet and novelist in the late nineteenth and early twentieth centuries. She seems to have the largest numbers of poetry web sites extolling her virtues for poems about woodpeckers. Here's her poem The Woodpecker in its entirety:

The woodpecker pecked out a little round hole
And made him a house in the telephone pole.

One day when I watched he poked out his head,
And he had on a hood and a collar of red.

When the streams of rain pour out of the sky,
And the sparkles of lightning go flashing by,

And the big, big wheels of thunder roll,
He can snuggle back in the telephone pole.

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?