mpox

“There never was a good war or a bad peace.” 2

Bud WiedermannAugust 18, 2024August 18, 20242 Comments

This quote from a Benjamin Franklin letter written 241 years ago still rings true. It's not hard to list bad traits of war, but I find that sometimes we overlook war's contribution to infectious disease outbreaks. Now we're seeing yet another example of this that could expand if not controlled.

Last week revealed a bundle of things to mention, I've tried to trim the list as best I could.

Oropouche HAN

Now the CDC has jumped on the Oropouche virus bandwagon with a new alert via the Health Alert Network. Most useful to front line healthcare providers is an approach for when to consider Oropouche infection more likely:

Consider Oropouche virus infection in a patient who has been in an area with documented or suspected Oropouche virus circulation within 2 weeks of initial symptom onset (as patients may experience recurrent symptoms), and the following:
- Abrupt onset of reported fever, headache, and one or more of the following: myalgia, arthralgia, photophobia, retroorbital/eye pain, or signs and symptoms of neuroinvasive disease (e.g., stiff neck, altered mental status, seizures, limb weakness, or cerebrospinal fluid pleocytosis); AND
- No respiratory symptoms (e.g., cough, rhinorrhea, shortness of breath); AND
- Tested negative for other possible diseases, in particular dengue. If strong suspicion of Oropouche virus disease exists based on the patient’s clinical features and history of travel to an area with virus circulation, do not wait for negative testing for other infections before contacting your state, tribal, local, or territorial health department.

As I've said previously, it's a clinical syndrome similar to dengue or chikungunya; note the absence of prominent respiratory symptoms. Cuba and Brazil travel has been associated with imported Oropouche in other countries; the disease is also experiencing a rise in Colombia, Peru, and Bolivia.

Similarly, we now have mpox reported from Sweden in a traveler returning from an area of Africa where clade I disease has been active. Details are scant, but it was certainly only a matter of time before this happened. Clade I seems to have a higher mortality rate than the more common clade II variant, but it's hard to get precise numbers, much less whether anything is different about the clade Ib variant now being seen. Transmission epidemiology seems to be slightly different than the clade II epidemic of a couple years ago which stemmed primarily from men who have sex with men. In this year's clade I iteration, infections also are being spread by heterosexual encounters, usually via sex workers, and also within households. Young children and pregnant women are at highest risk for complications including fatal outcomes. Like most sexually transmitted infections, public health measures are hindered by infected people not being willing to disclose their sexual contacts. In the Democratic Republic of Congo, the epicenter of the clade I outbreak, homosexuality is not officially illegal but societal norms in the DRC are not favorable to LGBT individuals.

Effective mpox vaccines exist for preventive measures, but a recent press release from the NIH had discouraging news about antiviral therapy. Tecovirimat, aka TPOXX, had been useful in clade II disease. Now, in a placebo-controlled randomized trial of almost 600 mpox-infected subjects in the DRC, tecovirimat outcomes for mortality and for time to improvement were the same as with placebo recipients. I'd like to see the actual study results, but I tend to trust NIH press releases more than most others. CDC has a nice update and map.

Parvovirus B19 Alert

Parvo B19 infection isn't a notifiable disease in the US, so if concern has arisen it usually means something dramatic is going on. This week CDC issued a HAN notice about this infection. The disease is well known to pediatric healthcare providers and to many parents as erythema infectiosum or fifth disease. It's a minor illness unless a pregnant person is infected, with subsequent risk of miscarriage or severe fetal anemia and non-immune hydrops fetalis. Individuals with chronic hemolytic conditions are at risk for aplastic crisis and severe anemia, and immunocompromised people have higher risk of complications. Read more if you need a refresher.

Is It Time for Universal Screening for Congenital CMV?

Last week's MMWR reported on the first 12 months' experience with Minnesota's universal newborn screening program for cCMV; it began in February 2023. 184 of 60,115 (0.31%) newborns screened on a dried blood spot had positive CMV results. Note that screening dried blood spots is less sensitive than other methods; 3 infants with cCMV with negative blood spot results and were picked up by other means. Buried in the report was the interesting finding that of 11 infants with permanent hearing loss, 4 passed their hearing screening test as newborns. Clearly we need more than universal hearing screening to identify at-risk infants. I look forward to further outcome data on Minnesota's program.

Dinner at the Sick Restaurant (apologies to Anne Tyler)

I like to think of myself as an adventuresome diner, but probably I would have drawn the line at these 2 delicacies I found at ProMED, the listserv I've used for decades.

Chicken liver sashimi is a new one on me, but now linked to an outbreak of campylobacteriosis in Japan. (You'll need Google translate for this one.) Perhaps slightly less disgusting is the idea of smoked non-eviscerated fish. Recent testing found a commercial product potentially contaminated with botulinum spores; thankfully no clinical cases have been reported. I've eaten sardines from a can. They also are non-eviscerated, but apparently the fish reported this week were capelin and exceeded the length allowable for packaging non-eviscerated fish. The product was produced and distributed by a company in Florida.

Covid

Meanwhile, let's not forget about our old friend. National wastewater levels are still up.

Levels might be tapering off in some parts of the country.

Meanwhile, clinical indicators suggest we're going to be seeing increasing cases the next few weeks at least. Here's an example with percent test positivity from the same link as above. It's a little higher than it was a year ago, though it's difficult to compare time periods since different factors now drive test-seeking behavior.

Meanwhile, if we can believe news reports (the FDA can't disclose approvals ahead of time), the new KP.2 variant-based mRNA covid vaccines should be available later this week. The Novavax vaccine presumably will be ready a little later. Timing for when to get the new vaccine should be based on individual considerations, including immunocompromised state, travel plans, and other factors. However, trying to predict the amount of covid activity over the coming months is only slightly better informed than a roll of the dice. Here's the current forecast from CDC.

Polio in Gaza

Not that it's unexpected, but a case of polio has been reported in a 10-month-old child in Gaza. This child would have been born just near the start of the new war and presumably was never immunized. Breakdowns in the health system as well as with clean water and sanitation are ideal for a reappearance of polio; it hasn't been seen in Gaza in 25 years. The UN has called for a "polio pause" to allow vaccine distribution. I try to avoid political statements in this blog, and I won't change that now, but I think my old friend Ben Franklin had it right about war.

Batesian Mimicry

To end on a lighter note, when I first saw this term I immediately thought of Norman Bates and "Psycho," perhaps Hitchcock's most famous movie. But no, it's not (spoiler alert) Norman mimicking his mother. This refers to Henry Lewis Bates' 1862 publication on butterflies in the Amazon. For an easier read, try this Wikipedia page. It explains my astonished update in last week's post that the mysterious black butterfly in our garden was in fact a dark variant of the easily recognized tiger swallowtail. Apparently it is an example of Batesian mimicry whereby a vulnerable butterfly species develops the ability to mimic a less desirable (to predators) butterfly. In this case, the tiger swallowtail mimics the unpalatable and toxic pipevine swallowtail. I mentioned last week that I had probably forgotten a lot about what I learned about butterflies in my childhood. I certainly don't remember anything about Batesian mimicry or dark tiger swallowtails. Needless to say, I've been down a rabbit hole all week about this. When I went back to my 3 texts on butterflies, all mentioned the black variant in the tiger swallowtail section but not in the sections on black-colored swallowtails where I was looking. As you can see below taken from "Mimicry and the Swallowtails," they are very different but in fact have subtle similarities that escaped me.

Summer Sleuthing 2

Bud WiedermannAugust 11, 2024August 11, 20242 Comments

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

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

More Oropouche Concerns

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

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

Mpox Redux

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

Persons at risk:

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

Benefits of Vaccination

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

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

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

Sniffles Status

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

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

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

Hieronymus Bosch

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

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

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

Red Book Renewal

Bud WiedermannMay 19, 2024May 19, 2024Leave a comment

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.

Lull or Spike – What Will Winter Break Look Like This Year?

Bud WiedermannDecember 10, 2023December 10, 2023Leave a comment

We continue forward into winter respiratory illness season, and I find myself wondering again how it will compare to prepandemic winter seasons. At that time, my annual wish had been that influenza and RSV peak activity would not coincide; if they did, healthcare facilities faced an overload. Now, covid is thrown into that same mix. Furthermore, in the prepandemic winter school breaks that occurred in the midst of flu season often seemed to put a pause in flu transmission that carried over into January. In today's world of infectious diseases, will this still be true, or could the increased travel and crowding result in a spike of respiratory infections? Perhaps we'll know in another month.

Bad Omen for Mpox?

Last week CDC released a Health Alert Network post about a new outbreak of mpox in the Democratic Republic of Congo (DRC). Although it is happening in a country far away from the US and not a common travel destination, I believe it's worth taking note of. It could impact health around the world, including in the US. To me this is more noteworthy than the respiratory illness surge in China that I mentioned last week because it may impact the US directly. The current DRC outbreak is a different clade of mpox that is potentially more virulent and could spread worldwide. We all remember the 2022-23 outbreak resulting in mpox becoming endemic in the US and a particular hazard for men who have sex with men.

The previous outbreak was caused by clade 2 mpox, generally endemic in western Africa. The new DRC outbreak is clade 1 that historically has been more common in central Africa and may cause more serious infections generally including higher mortality. What is different in the DRC now is that human to human transmission has been documented, included sexually-transmitted disease. So far clade 1 has not been seen in the US, and the alert mentions that none of the 150 US isolates from 2023 undergoing testing (a 12% sampling) have been clade 1. It is likely that the same countermeasures that have been effective for the clade 2 outbreak, including vaccine and antiviral therapy such as tecovirimat, brincidofovir, and vaccinia immune globulin, will be effective for clade 1 disease. Now is a good time for healthcare providers to brush up on clinical diagnosis of mpox and counsel high risk individuals to seek vaccination.

Remember Eleanor

For most of my career I have kept and updated a list of Bud's Laws, now a compilation of 10 aphorisms designed to trigger recall of some key bits of medical knowledge for clinicians. One of them is "Remember Eleanor" to trigger the fact that tuberculosis has many clinical presentations, some outside of the usual fever, pneumonia scenario. The Eleanor in the aphorism refers to Eleanor Roosevelt who died of tuberculosis in the 1960s. Her physicians had been treating her for aplastic anemia; TB was finally diagnosed when it was too late for treatment to be effective (plus she apparently had drug-resistant TB!). Whether her physicians actually misdiagnosed her aplastic anemia or the steroids they administered for that just reactivated latent TB isn't clear to me.

A recent MMWR report of neonatal death following failure to diagnose mother with active TB is a heartbreaker. Mother did have risk factors for tuberculosis and concerning symptoms of insufficient weight gain and hyperemesis dismissed as due to pregnancy, plus chronic cough written off as gastroesophageal reflux. Mother wasn't evaluated for TB until her newborn became seriously ill in the third week of life, ultimately developing septic shock and dying at 6 weeks of age.

TB diagnosis is always easier in retrospect; please keep it in mind especially for individuals with risk factors.

Respiratory Virus Tracking

Clearly CDC is messing with me. Their cutoff for weekly data summary is Friday, but they don't post the updates until the following Monday. So, my blog post on Sunday will be a week off.

Still, nothing is going to change too much in a week to alter clinical practice during winter respiratory illness season. Here's a few details from the latest CDC graphics.

Remember that the graphic above will capture other illnesses besides flu, but it's a pretty good indicator for flu season. RSV hospitalizations in the 0 - 4 year age group still appears to be rising nationally.

Percent positivity of RSV tests may have peaked already, too early to be certain but that could be a good sign.

Covid wastewater levels continue to be high and rising.

Note that you can visit this site and see a breakdown by regions of the country; currently the Midwest has the highest levels.

Managing Mild Pneumonia in Children

I welcome comments to this blog and I answer them routinely - unfortunately subscribers don't get an email notice when I do so, you'll need to keep track of comments when you are looking at the site.

This past week I received a comment from Dr. Rebecca Carlisle who practices mostly in a pediatric urgent care setting. I thought it was worth answering in a regular post because it brings up an issue I think most pediatric practitioners are facing now. She wrote, "I’ve been seeing a lot of kids-ages 4 to young adults with terrible sounding lungs-wheezing/rales-not really responding to nebs. I’ve been chalking it up to “viral pna” but a couple times have started Azithro (one of my least favorite medicines bec I think it’s overused in the adult population).... Your post mentions that tx doesn’t usually help, but maybe in early illness? Any elaboration on that and should I be trying more Azithro, never Azithro?"

It would be great if we had a guideline that helps us with managing pediatric community acquired pneumonia (CAP). Of course we did have one from the Infectious Diseases Society of America, but it was written in 2011 and has been archived, meaning it is no longer accurate. They are working on a new guideline, too late to help us now. WHO also has a guideline but that is geared for managing CAP in resource-poor countries and not that helpful for a US population.

Regardless of whether we have current guidelines or not, probably the most important consideration in management of mild CAP in children is knowing what pathogens are circulating in your community. In the midst of flu season. rapid testing for influenza should be obtained if treatment is considered, whether it be for mycoplasma, other bacteria, or influenza. Azithromycin likely is still the drug of choice in this age group, given that mycoplasma is more common in the slightly older child and it may have some activity against pneumococcus, depending on local resistance patterns.

The real problem with azithromycin in this circumstance is that it may have little to no effect on the course of mycoplasma lower respiratory disease. Randomized placebo-controlled trials in children from decades ago showed no difference between erythromycin treatment and placebo outcomes. A 2015 Cochrane review reinforced this: "In most studies, clinical response did not differ between children randomised to a macrolide antibiotic and children randomised to a non‐macrolide antibiotic. In one controlled study (of children with recurrent respiratory infections, whose acute LRTI was associated with Mycoplasma, Chlamydia or both, by polymerase chain reaction and/or paired sera) 100% of children treated with azithromycin had clinical resolution of their illness compared to 77% not treated with azithromycin at one month." The authors called for high-quality RCTs to answer the question, but the problem is that, since mycoplasma LRTI is self-limited, the sample size needed for a definitive study is quite large, probably prohibitively expensive unless a pharmaceutical company comes out with a new macrolide where future sales might warrant investment in such a trial.

For now, chest radiographs aren't indicated for mild pediatric CAP, and diagnostic testing should be limited to treatable infections such as influenza or for situations where elderly or immunosuppressed close contacts could benefit from knowledge of the child's infection. Azithromycin treatment of mild CAP in the school-aged child probably should be the exception rather than the rule. It's not a never event, just something to be considered based on the child/family individual concerns. Just my opinion.

TB in Literature

Speaking of Eleanor, probably your holiday vacation reading list isn't full of books about TB, not a particularly uplifting topic. My favorite TB novel by far is Thomas Mann's The Magic Mountain, but it does require a bit of diligence to make it through. If you're interested in a shorter novel where TB is featured, think about Penelope Fitzgerald's The Blue Flower. Her other 8 novels are all great as well.

To Rake or Not To Rake

Bud WiedermannOctober 29, 2023October 29, 2023Leave a comment

A lot going on in the world of infectious diseases this past week, enough to challenge my ability to sort out and explain the key points. That's probably why my mind, and eyes, keep drifting to the window next to my desk. The neighborhood leaf pickup is coming any day now, and many leaves cover the ground. The number of fallen leaves is still far less than remain on the old maple tree just outside the window. Yes, it's too early to rake, I would just need to do it again in another week.

Here's my stab at summarizing recent ID events.

RSV and Nirsevimab Shortage

CDC issued a HAN (Health Alert Network) advisory statement on October 23 with a plan for prioritization of nirsevimab use in the face of limited supply.

I won't attempt to summarize everything here because the recommendations are detailed and depend highly on individual circumstances impacting nirsevimab access; please read the advisory. The 100 mg dose is the most severely restricted, and practitioners should not combine 2 50 mg doses to make up the difference because you are essentially depriving 2 younger/smaller children from access in order to treat 1 other child. Note that palivizumab (Synagis) is still available and is the go-to product for infants 8 - 19 months of age, the same as in previous RSV seasons.

At last week's Advisory Council on Immunization Practices (ACIP) meeting (see more below), the nirsevimab company representative completely avoided answering a request to provide details for the cause of the shortage, other than to invoke a supply versus demand problem. I'm hoping those details appear down the road so mistakes like this can be prevented in the future.

Remember COVID-19?

I hope nobody has forgotten, but never underestimate our short attention spans. Thankfully things are relatively calm compared to pandemic times.

I felt the lay press got things a bit wrong when reporting findings of a study by FDA and others regarding safety of monovalent covid vaccines given to children before early 2023 (i.e. NOT the current vaccines). Unfortunately the report has not been peer-reviewed, but it appears pretty sound from my brief reading. The risk of myocarditis/pericarditis in adolescent boys was pretty much the same as we've heard about all along. Also mentioned was seizure risk in younger children, and this part was over-hyped by some news agencies. The association merits further study, but currently is very uncertain: "...seizures/convulsions signals were detected following vaccination with BNT162b2 and mRNA-1273 in children aged 2-4/5 years. However, in a post-hoc sensitivity analysis, the seizures/convulsions signal was sensitive to background rates selection and was not observed when 2022 background rates were selected instead of 2020 rates." The exact numbers were 72 children with seizures, most fulfilling the case definition of febrile seizures, out of 429,119 doses administered to that age group. Thus, it is very close to the background rate of febrile seizures, without vaccination, in that population.

Tripledemic Status

Well, more like a weak monodemic now, with RSV still the only one of our RSV/Influenza/Covid triumvirate to appear in appreciable numbers in most places. RSV-NET shows some hospitalizations in young infants below, but note that hospitalizations are only the tip of the iceberg for infections.

FluView activity is similarly low in most locales.

Biobot wastewater tracking for covid remains low.

New Immunization Schedules for 2024

As mentioned above, the ACIP met October 25 and 26 to cover a variety of subjects and reveal proposed immunization schedules for 2024 which were approved. This approval is awaiting some tweaking and then final signoff by the CDC director. The new schedules will have many new options, which is both good and bad. It's always nice to have more choices, but at the same time those choices create new complexities that aren't easy to explain; CDC doesn't have a great track record for making recommendations understandable. Potential changes include vaccines for COVID-19, influenza, meningococcus, mpox, pneumococcus, polio, and RSV (monoclonal antibody and vaccine). Release is planned for January 2024, earlier than usual.

Pediatric healthcare providers should take note of proposed new mpox vaccine recommendations, now just applying to age 18 and older but likely to eventually include ages as young as 12 years once NIH trials are completed, perhaps as early as next year. Like most outbreaks/epidemics/pandemics, mpox has evolved from the 2022 epidemic into a 2023 endemic problem now at about 1-4 cases per week on average.

Because of this, and the fact that a highly effective and safe vaccine is available, the new guidelines likely will recommend immunization for those at high risk:

Gay, bisexual, and other men who have sex with men, transgender or nonbinary people who
in the past 6 months have had one of the following:

A new diagnosis of ≥ 1 sexually transmitted disease
More than one sex partner
Sex at a commercial sex venue
Sex in association with a large public event in a geographic area where mpox
transmission is occurring
Sexual partners of persons with the risks described in above
Persons who anticipate experiencing any of the above

We will also see new recommendations for pneumococcal vaccine now that a 20-valent pneumococcal conjugate vaccine is approved. PCV13 will phase out and infant immunization will include just PCV15 or PCV20. The 23-valent pneumococcal vaccine also will phase out, except perhaps for a stockpile kept for use in immunologic diagnostic testing.

Covid vaccination will be a little easier for young children, with clarifications for which vaccines to use for children undergoing age transitions in the midst of vaccine cycle as well as greater allowance for interchangeability of vaccines (e.g. administering Pfizer vaccine when previous vaccine was Moderna) for children 6 months through 4 years of age:

COVID-19 vaccine doses from the same manufacturer should be administered whenever recommended. In the following circumstances, an age-appropriate COVID-19 vaccine from a different manufacturer may be administered:

Same vaccine not available at the vaccination site at the time of the clinic visit
Previous dose unknown
Person would otherwise not receive a recommended vaccine dose
Person starts but unable to complete a vaccination series with the same COVID-19 vaccine due to a contraindication

The changes for meningococcal vaccination are the most confusing. A pentavalent vaccine was approved recently by FDA for use as a 2-dose regimen for ages 10 through 25 years. The confounding factor for meningococcal vaccination is that the disease is relatively uncommon, particularly for serogroup B where we see only a handful of cases annually. Furthermore, vaccine immunity wanes fairly quickly following group B vaccination, and we are potentially faced with healthcare offices needing to stock 3 different meningococcal vaccines to cover all circumstances. Here are the current recommendations for meningococcal vaccination:

Here's a look at the serogroup distribution by age (June 2023 ACIP meeting, presentation 3 slide 9 for meningococcus):

How best to add in the pentavalent vaccine? Just using that vaccine alone isn't a good idea. Trying to incorporate immunization against group B into the current schedule that starts at age 11 is likely too early to be effective. ACIP has been struggling for several months to come up with a plan for meningococcal vaccination that takes into account the relative rarity of the disease as well as the need to provide a pragmatic plan that can be implemented in diverse healthcare settings. They focused on 3 policy questions that were debated by working groups over the past several months:

PICO 2 was deemed unfavorable for a variety of reasons. We are left with deciding how best to use the pentavalent vaccine for situations 1 and 3, knowing that stocking 3 different meningococcal vaccine products may not be feasible for many practice settings. I expect continued tweaking of the options before we see the final guidelines in January, but it appears that routine immunization will still be recommended at age 11-12 years with second dose at 16 years. Group B vaccination options will variously allow use of the monovalent or pentavalent products, but it may be that the pentavalent product will be recommended for a slightly different age range (16 - 23 years) than what was approved by FDA (10 - 25 years). Regardless, the Menactra vaccine (covering groups A, C, W, Y) will be withdrawn so at least some simplification there.

A concluding disclaimer to this section: all we have now from ACIP are proposed changes. They are not approved and very likely will undergo some changes before we see them in print. Please don't act on the above until we have the updated guidelines from CDC.

Staring Out the Window Again

You can perhaps understand my tendency to wander after reading the section above. The meningococcal vaccination options are almost endless, and I didn't necessarily agree with the way the discussions were going at the ACIP meeting.

The title of this posting is a lame riff on Shakespeare, and his Sonnet 73 mentions leaves prominently. However, it is primarily a poem about aging and I didn't necessarily want to be reminded of that! I found a more playful ode to autumn in a poem by James Whitcomb Riley; he has a children's hospital named after him although he was a very complex individual who suffered from alcoholism and wasn't exactly a model citizen. His poems often are written with a child-like voice and lend themselves well to reading aloud.

"But the air’s so appetizin’; and the landscape through the haze

Of a crisp and sunny morning of the airly autumn days

Is a pictur’ that no painter has the colorin’ to mock—

When the frost is on the punkin and the fodder’s in the shock."

Tag: mpox