Patrick O'Brian – Pediatric Infection Connection

The 33rd edition of the American Academy of Pediatrics' 2024-2027 Report of the Committee on Infectious Diseases, aka Red Book, arrived online (and on my doorstep) recently. This latest edition adds about 100 pages to the 32nd edition, even as many sections were combined or shortened. More than annual spring cleaning, this is a renewal effort for me that has become an enjoyable triennial task for me. Although the early pages provide a brief summary of changes (total 222) from the previous edition, I operationalize this by having the new Red Book at my side always, looking up every clinical situation I encounter in reading or in patient care. Not surprisingly, even after doing this for maybe the next year, I still won't remember everything, but I'll know when and where to look. Remember also that the Red Book advice is in many instances a set of consensus opinions that are subject to author bias, even with extensive review and editing. Nothing is etched in stone, and individual patient circumstances may require deviation from general recommendations.

In the meantime, let's look at what's been going on in pediatric infectious diseases recently; this isn't in the Red Book.

A New Look CDC Website

Our friends at CDC announced a new look to their website with a focus on reducing clutter and making access easier. After my first series of run-throughs, I think they are well on their way to that goal. It's worth your while to view their 2-minute YouTube video describing the changes.

Bird Flu News

Still no reason to increase fears of the next human pandemic, but plenty going on. The US Department of Agriculture (they should talk to their CDC colleagues about reducing website clutter and improving navigation!) updated beef safety with some new studies. First, USDA tested ground beef samples from stores in states known to have influenza A H5N1 present in cattle; all were negative by PCR, although they don't mention how many samples were tested. Second, they performed studies on cooking ground beef spiked with Highly Pathogenic Avian Influenza "surrogate" virus (they don't specify details or numbers). Cooking the burgers to medium (145 F) or well done (160 F) eliminated all live virus. Rare (120 F) cooking "substantially inactivated" the virus, whatever that means. I'm looking forward to results of another ongoing study of PCR testing of muscle samples from cows who were culled due to "systemic pathologies" which should go a long way in helping understand if there is any reasonable risk of transmission of H5N1 in raw beef.

Meanwhile, in the latest update there have been no new state detections in domestic livestock since April 24. Bird infections remain a major problem as judged from USDA's main avian influenza website.

FDA provided a little more detailed information than did USDA. They found no viable virus in 297 pasteurized dairy products tested and confirmed by egg inoculation studies which should be highly sensitive.

Things are improving, but more proactive testing, especially of asymptomatic wild and domestic animals and high-risk humans such as poultry and dairy workers, is needed to stay ahead of any epidemic trends.

MMWR Trifecta

I'm not a big horse-racing fan, though I did watch the Preakness this weekend. This week's (May 16) MMWR hit a trifecta for me in that 3 topics are worth mentioning, so here's a quick look.

Measles: We have a detailed report of the outbreak associated with the migrant shelter in Chicago, spread over February through April 2024. Here's the quick overview:

The key take-home points: 1) Most of the 57 cases occurred in unvaccinated individuals; 2) active case-finding and a mass vaccination campaign (882 residents were vaccinated) likely averted a larger disaster.

I wish we had similar reporting from the Florida public school outbreak, apparently managed very differently but we know nothing about what was done. I can still find only a March 8 update that sounds mostly like a political statement.

Clade I Mpox: This clade I outbreak continues in the Democratic Republic of Congo and, compared to the clade II strain that caused the global outbreak in 2022, this clade I seems more virulent, with higher morbidity and mortality than seen with clade II (this was known prior to this outbreak). Again, here's the big picture:

While the numbers appear to be trending downward in the latter dates on this graph, this could be due to delays in reporting.

Age distributions are alarming for pediatric healthcare providers though clearly are influenced by social factors present in the DRC and might not apply to any US cases if we do see global spread.

The Jynneos mpox vaccine is effective against both clades, and high-risk individuals in the US should be vaccinated. The newly revamped CDC mpox site is a good example of how they've improved the look and ease of navigation. Providers should access this again to be sure they have offered vaccine to those at risk.

Polio: This was an update on progress towards polio eradication and is a good news/bad news report. The good news is that wild-type polio infections appear to be decreasing over the period January 2022 to December 2023. Wild type polioviruses types 2 and 3 (WPV2 and WPV3) have been eradicated, and only WPV1 continues to circulate but just in Afghanistan and Pakistan. In 2023 there were only 12 cases of WPV1 identified, compared to 22 in 2022, a decrease even with more extensive sewage screening in 2023. The bad news is that circulating vaccine-derived polio (cVDPV) cases, from live polio vaccine, continues to be a problem. The number of cases decreased (881 in 2022 to 524 in 2023) but the number of countries affected increased from 24 to 32. The vast majority of these are cVDPV1 and cVDPV2. WHO has newer and more effective vaccination strategies to eliminate both wild and vaccine-derived strain infections, but implementation is difficult.

Books - Red and Other Colors

Regular readers of this blog know that I'm an avid reader. I'm not an avid book collector, however. I try to keep a relatively static number of books in the house, requiring donating old books to my neighborhood public library's used bookstore as I acquire new ones (my last trip to a used bookstore resulted in 11 additions to my sagging bookshelves). However, I'm now reminded that I have 3 collections that I don't recycle from my shelves.

First is the Red Book. I own all editions dating back to 1961, the 13th edition, plus the 6th edition of 1944. I've been unable to find the remaining 11 editions, probably because I'm not as adept at used bookstore searches as I am at PubMed searches. I'll keep trying. Three pediatric infectious diseases giants, Drs. Larry Pickering, Georges Peter, and Stan Shulman, wrote a nice review of Red Book history in 2013.

My other 2 non-recyclable book collections are very different. One is the Audrey/Maturin series of nautical novels by Patrick O'Brian. I also own several of his lesser works. I'm not sure why I hang on to all of those; perhaps it's because my initial attempt at reading one was quickly abandoned due to boredom. Years later I picked it up again and was hooked. My other collector fascination is the Parker noir series by Richard Stark, a pseudonym of Donald Westlake. I lack many in the series which I could easily buy as newly issued printings, but I prefer to prowl used bookstores for older copies. I haven't happened upon an old one in years, but hope springs eternal.

We seem to have settled back into the good old days of infectious diseases and outbreaks, always something going on but at least nothing on the level of the past 3 years. Certainly we'll see an upswing in covid sometime in the coming months, but in the meantime I will try to return this blog to something approaching normality.

Short Antibiotic Course for Community-Acquired Pneumonia in Children

A group of Chinese investigators, working with McMaster University experts in evidence-based medicine, reported a meta-analysis looking at treatment duration in randomized controlled trials of antibiotics for pediatric CAP. Let me say from the start that this study is an excellent example of how to perform a high quality meta-analysis. I came to that conclusion before I realized that the McMaster group was involved, in particular Gordon Guyatt who is one of the world's leading researchers in EBM methodology.

The group defined short-term treatment as 5 days or less and found that shorter duration did not seem to alter outcomes compared to longer treatment. Here is one of the Forest plots looking at treatment failure of 3 or 5 days of antibiotics versus 5, 7, or 10 days:

This is one of many forest plots (also known as blobbograms, don't you love that!) including multiple subgroups that together provide reassurance for short-course therapy for CAP. The authors spent considerable time looking or sources of potential bias, somewhat difficult because each of the included studies had differing definitions and methodologies.

The children in these trials had relatively mild CAP, so the results shouldn't apply to those with more severe CAP. Also, It is likely that a large proportion of study subjects had viral infections. As the authors mention, "... it is usually extremely difficult to distinguish between viral and bacterial CAP." Still, the takeaway message should be to consider short (or no) antibiotic therapy for mild pediatric CAP.

Human Papillomavirus Transmission from Pregnant People to Their Neonates

Investigators from multiple Canadian institutions reported a prospective cohort of 1050 pregnant persons and their newborns with regard to HPV infection rates in the mothers, along with HPV detection in placentas and rates of positivity in their infants followed for a 6-month period. Note that the study recruited mothers early in pregnancy in the time period of 2010-2016. The bottom line was that 40%(!) of mothers had detectable vaginal HPV, but only 92/860 (10%) of tested placentas were positive. Detection of HPV from any site (conjunctival, oral, pharyngeal, genital) in newborns at birth or at 3 months of age was positive in about 7%, but no infant was positive at 6 months of age at any site.

This is a nice study and is somewhat reassuring that HPV transmission from mothers to infants in utero or perinatally is not a large problem. Of course, having seen innumerable infants with tracheal HPV, I can vouch that even an uncommon event like perinatal HPV transmission can result in severe consequences.

'Demic Doldrums

Please excuse my stretch to find an alliteration for this topic. Until we see the next covid wave, I liken this time to the doldrums. If you, like Jack Aubrey*, command a ship in the early 19th-century British Navy, the doldrums are to be feared; an absence of wind means your ship is stalled. It's not easy to row a 3-masted vessel in the ocean. However, a pandemic doldrum is a good thing. I'll include some 'demic doldrum postings as a semi-regular feature in upcoming blogs.

This past week had a few covid highlights worthy of mention. First, investigators at the University of Warsaw, Poland, reported 3- and 6-month echocardiographic evaluations in 172 consecutively diagnosed children with Multisystem Inflammatory Syndrome in Children. All of the subjects were asymptomatic from the time of their MIS-C hospital discharges. Results were quite good, even in those with initially severe cardiac involvement.

Along similar lines, we have some new data on safety of the Pfizer covid vaccine with numbers on myocarditis/pericarditis rates. It's a US commercial claims database analysis from the FDA and other organizations (but no contribution from Pfizer, so less chance of bias) and covers 3 million children 5-17 years of age. It looked at rates after both the primary series and after a third vaccine dose. Out of 20 different adverse events monitored, only myocarditis/pericarditis showed a safety signal but just in children in the 12-15 and 16-17 year age groups. The average rate for this complication was 39.4 events per million vaccine doses and tended to occur about a week after the primary series. The investigators were able to perform medical record reviews on only a subset of the events to verify diagnoses. This study is an example of the type of post-marketing data we need to continue to follow vaccine recipients for adverse events and is encouraging that nothing new is turning up so far.

We also have evidence of progress on the long covid front, more appropriately termed PostAcute Sequelae of COVID (PASC). We now have a better case definition. That may not sound like a big deal, but for something this complicated a good case definition is essential to figuring out diagnostic and management trial design and best strategies. A group from multiple institutions in the US developed a scoring system based on study of almost 10,000 adults. Signs and symptoms found to be significant enough to include in the scoring include postexertional malaise, fatigue, brain fog, dizziness, gastrointestinal symptoms, palpitations, changes in sexual desire or capacity, loss of or change in smell or taste, thirst, chronic cough, chest pain, and abnormal movements.

Meanwhile, it's time to pay attention to the southern hemisphere, just as we do for influenza, since it could be a harbinger for what we'll see in a few months. We don't have the same level of monitoring as early in the pandemic, but I will keep my eye on Australia, where cases are rising in almost all states though still at a low level.

Lastly on the covid front, variant studies such as those in the UK continue to show we are living in an XBB variant world. I'm also keeping my eye on a new one, EM.1.

*Jack Aubrey is the fictional British naval officer appearing in 20 (+1 uncompleted) novels by Patrick O'Brian. I've read all the books and was pleased to see the first in the series recommended for summer reading by the Washington Post's (and fellow Silver Spring resident) Michael Dirda. The books take a little work, a lot of unfamiliar terminology and details to get through, so not quite the easy beach read. You may be more familiar with the movie Master and Commander which was actually a combination of events from 3 of his books.

Whatever you're up to this summer, try to make room for curling up with a few good reads.

Tag: Patrick O'Brian

Red Book Renewal