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At this time of year many of us turn our thoughts to ancient times, whether to the second century BCE (for the Maccabees and Hanukkah), the first century CE (Jesus and Christmas), or other wintertime traditions even dating back to 10,000 BCE and celebrations related to the winter solstice. A recent article turned my thoughts to a little earlier time in antiquity, around 7000 BCE. But first ....

WHO Cholera Update

New reporting from WHO is a bit depressing, given that cholera is controllable with good sanitation, plus we have effective vaccines and treatments available. Worldwide cases this year, as of November 24, increased 37% compared to last year. So far, we are up to 733,956 cholera cases and 5162 deaths from 33 countries across five WHO regions. WHO cites multiple factors for the increase, including vaccine shortages, climate change, conflict, mass displacement, and natural disasters including floods.

Avoid Bats**t

Among other things to avoid, bat guano is not a healthy choice. Researchers at the University of Rochester reported 2 fatalities from histoplasmosis traced to bat guano used as fertilizer for marijuana plants. Both were adults with underlying medical conditions. Infection with Histoplasma capsulatum usually is asymptomatic but can become symptomatic and severe with massive exposure or in persons with high risk factors such as immunosuppression.

Avian Flu

Though not wanting to contribute to over-dramatization of our ongoing saga of influenza A H5N1 in poultry and cows, the count of human infections is still increasing slowly, now at 64 cases nationally. Most importantly, we still have no evidence of human-to-human transmission, and it remains mostly a relatively mild infection in humans. Probably the biggest impact we all see is in the price of eggs.

This past week we saw confirmation of severe disease in a human. It occurred in an adult with significant underlying medical conditions who had exposure to dead and ill birds in a backyard flock. Genomic sequencing of the person's flu strain suggested its likely origin as being from avian as opposed to bovine origin. Front line health care providers should take this as a reminder to inquire about exposure to birds, both wild and domestic, and to cows as a routine part of evaluation of flu-like illness.

Please Consider Antiviral Therapy for Influenza

This past week I consulted on a child hospitalized with pneumonia who had a mild respiratory illness testing positive for influenza about 10 days previously. The child hadn't received flu vaccine this season, and the urgent care physician who diagnosed flu did not prescribe treatment for influenza. I don't know if oseltamivir treatment would have prevented the hospitalization, which could have been a separate illness, but the case did remind me that many providers are not using the tools at our disposal to help prevent adverse outcomes from flu.

A recent multicenter study revealed that about half of children hospitalized for influenza did not receive antiviral therapy. Various factors were associated with receipt of therapy.

As a reminder, we have a total of 4 drugs approved for treatment of influenza: oseltamivir (Tamiflu) and baloxavir (Xofluza) are oral agents. Other options are intravenous peramivir and inhaled zanamivir. While anti-influenza treatment works better in the first 2 days of illness, there is still benefit from treatment started later. Also, there isn't much point in testing for influenza if you're not going to treat it!

WRIS

We are well into winter respiratory infection season now, largely driven by RSV and influenza. I'd encourage everyone to look into the status for your own location at the CDC website.

Ancient Times: The Origins of Syphilis

We've seen a lot of controversy (and shouting) the past few years regarding the origins of covid. A recent archeologic study on the origins of syphilis and other treponemal diseases caught my eye. Although I'm not aware of any shouting matches around this origin controversy, it's noteworthy that the answer still is a bit up in the air. The study used genome analysis of multiple specimens and provides convincing evidence that treponemal diseases originated in the Americas. Their findings, along with many others, suggests that we can blame Columbus for bringing syphilis to Europe but not vice versa as some have postulated.

I should remind everyone that there are 3 forms of human disease caused by Treponema pallidum: T. pallidum pallidum (syphilis), T. pallidum pertenue (yaws), and T pallidum endemicum (bejel). (Pinta, the mildest human treponematosis, is caused by T. carateum.)

Regardless of whether you celebrate this holiday season based on traditions from the time of winter solstice recognition and the origins of treponemal disease or the more recent and more common religious and secular traditions (remember Festivus?), I wish everyone a wonderful time the next few weeks.

Courtesy of https://commons.wikimedia.org/wiki/File:Festivus_Pole.jpg.

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?

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.