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Published on Leave a comment on Happy World Leprosy Day!

I'm not sure I'd put this in the same celebratory category as a new year's event (January 29 is Vietnamese new year and Chinese new year for 2025), but it is noteworthy. WHO publicizes this day, and it might surprise some in the US that we had 369 new US cases detected in 2023, including 4 children. Here's a global map:

Leprosy still is one of the most stigmatized diseases in the world, fed by rumor and superstition. WHO is a good source for factual information. Speaking of WHO ...

US Quits WHO - What Does This Mean?

Well, this executive order doesn't mean anything immediately, assuming the new administration doesn't somehow violate the agreement for giving a year's notice to WHO before leaving. The US is obligated to pay for 2025. I have no direct experience with WHO, but it is well-known to be a large bureaucracy with the usual ponderous systems that this brings. I did find some better information from one of the many information sources I read, this one written by epidemiologist Dr. Katelyn Jetelina. She previously worked at WHO in Geneva, and her January 23 post provides more insight into how the loss of US funding for WHO might impact world health. She documents many problems with the WHO, but also provides a stark look at what the loss of US funds could portend. The US is the largest donor to WHO.

I'm hoping cooler heads will prevail and this exit won't go through.

MMWR Disappears

I've been subscribing to CDC's Morbidity and Mortality Weekly Report for more than 40 years, way back to when the paper copy came to me in snail mail every week. The communications embargo for health information, detailed in a memo by the acting Secretary for HHS, put a hold until February 1 on federal agencies issuing any information that hasn't been reviewed by a presidential appointee. The memo does allow for exceptions that include critical information, again requiring some sort of political appointee approval.

The MMWR isn't particularly controversial in my mind. I read it every week, but I suspect most healthcare providers don't keep it on their nightstands, or whatever that equivalent is in today's digital world. As of now, the current issue is listed as January 16, with nothing about a January 23 edition. Presumably we will miss January 30 as well.

I'm not so worried about this now, I'm sure we'd hear if we need to take any urgent action with bird flu or other emergency, but I am concerned about whether political censorship will affect the credibility of this information in the long run. I can still remember the chaos early in 2020 and the insistence by some of the value of hydroxychloroquine, ivermectin, and even bleach as effective treatments.

And, speaking of avian flu ...

Avian Flu Update (without CDC)

The Infectious Diseases Society of America broadcast a bird flu webinar, usually done in conjunction with CDC, but this time CDC wasn't mentioned in the title and none of the speakers had CDC appointments. I was able to attend the session in its entirety, and the recording and slides are available to everyone. In spite of the official CDC absence, the speakers were bona fide experts, and I learned several things.

The molecular difference between highly pathogenic avian influenza and low (not lowly) pathogenic strains (slide 6):

Recent global spread of HPAI by wild birds (slide 11):

Spread to dairy cows facilitated by excellent replication in mammary glands and transmission among cows mainly via milking machines (slide 16):

Experience in California suggests that conjunctival swabs may have higher yield of H5N1 than nasopharyngeal swabs (slide 37):

Remember that conjunctivitis is common (80%) in current human cases of H5N1 but is not a prominent feature of seasonal influenza.

Sequencing of strains from human cases in California suggest that the human cases arose by independent cattle-to-human infection events (slide 40), explained by the red dots below appearing in separate phylogenetic trees:

Also some discussion ensued about various testing options. The short version is that none of the tests are approved for conjunctival specimens, and the sensitivity of various tests to identify influenza A H5 is uncertain. Also unknown is whether testing costs in commercial labs would be covered by various insurance plans.

The penultimate presentation was by Bethany Boggess Alcauter, PhD, from the National Center for Farmworker Health. She provided a unique perspective that enlightened me greatly. It starts with slide 72. It was very clear that farmworkers have difficult jobs with little labor protections (below is slides 75-78):

One can easily imagine how tough it is to monitor and manage infections in these workers who now have the added burden of being more targeted for deportation.

A final presentation by Dr. Richard Webby from St. Jude Children's Research Hospital summed up in slides 86 and 87 the current understanding of H5N1 evolution and how difficult it will be to predict the future:

Antibiotics Can't Beat Cold Steel for Appendicitis

Moving away from various pandemic and political concerns for a moment, a new randomized controlled trial suggests that medical therapy alone is inferior to appendectomy (aka appendicectomy in the article) for management of uncomplicated appendicitis in children 5-16 years of age. This was a multinational study at 11 sites (2 in the US) that enrolled a little over 900 children with suspected non-perforated appendicitis.

Prior studies have suggested antibiotic therapy alone is an acceptable management pathway, and I suspect we haven't heard the last on this issue. For now I'd go with surgical intervention as the better alternative.

WRIS

With the muzzle on federal authorities releasing new data, I was interested to see what my usual information sites had available to me this week to monitor winter respiratory viral infection activity. I'm happy to report that the CDC's Respiratory Illnesses Data Channel was updated on Friday as per usual.

The NREVSS Dashboard also was updated (the cutoff date is January 17, but this diagram has additional data compared to last week's report).

I'm not subscribing to any crystal ball methods for predicting how WRIS will progress; I've seen some intimations that covid will be mild this winter, but I worry that some folks are trying to fit covid into a seasonal virus pattern which so far we've learned is not true.

Any bets on whether we'll see MMWR this week?

Happy Year of the Snake! Sức khỏe dồi dào

https://chus.vn/year-of-the-snake/

Published on Leave a comment on Word of the Week: Conundrum

I was very underwhelmed by Oxford University's recently announced Word of the Year. Listening to last week's FDA VRBPAC discussion of RSV vaccines, another word kept cropping up time after time. More on that later.

Covid Updates

I had mixed feelings when I learned that the Netherlands had started a Long COVID Kids Choir, apparently also active in the UK and the US. On the one hand, it's great that these children have on outlet to express themselves, but on the other hand it reminds me how little we know about this condition.

On a more uniformly upbeat note, new data are available for effectiveness of the Pfizer XBB vaccine in children 5 - 17 years of age. This was a retrospective study from Kaiser Permanente Southern California looking at acute respiratory infection visits from October, 2023, through April, 2024. Because of the study design (standard test-negative case-control study) we only have odds ratios to describe results; number needed to vaccinate can be estimated from odds ratios with fudge factors, but I'm reluctant to go there. Here's the summary:

Basically, the vaccine was very effective in preventing hospital admission and ED/urgent care visits in this age group.

Temporal Thermometers Not the Greatest

Temperature measurement using temporal thermometers is pretty much a tradeoff - convenience versus accuracy. A new study from 5 EDs in a single system (apparently Mass General but hard to tell from the article) looked at around 1400 children who had both temporal and oral or rectal temperatures measured at the same time (within 30 minutes). The findings are summarized here; note mean discordance of about 1.5 F. Researchers found that age < 12 years was was associated with discordance.

The authors found that self-reported race was not a risk factor, important because skin color could plausibly affect temporal measurements. As an interesting aside, Black children were more likely to have temporal temps only, even correcting for severity of presenting complaint.

Avian Flu

I'm keeping a wary eye on new progress, mostly because I'm worried that not enough resources are being devoted to monitoring the situation. One new report provides helpful information. Two dairy farms voluntarily allowed investigators to look at prevalence and spread of influenza A H5N1 in their settings. Here's the "graphical abstract::

The authors mention the rarity of these types of studies possibly due to farm owners' worries about harm to their businesses from publicity about avian flu spread in their dairies.

CDC provided genetic sequencing information about the virus infecting the child in California who apparently has no known avian flu exposure risks. Analysis suggested that the strain was very similar to those previously seen in dairy and poultry farms as well as in humans, but they were unable to perform complete sequencing that could have allowed further tracking of the source of this child's infection. I guess due to privacy concerns, we have very little clinical information about this case. I'm even wondering how the child's strain came to be tested for H5N1 in the first place since not every influenza A detection undergoes further testing.

Regardless of uncertainties, these most recent reports do not suggest we need to heighten concern for human to human transmission of A H5N1.

DRC Mystery Disease

Shortly after my post last Sunday, WHO released a new update with a few more details but still no big findings. I can't even find their case definition anywhere. The initial statements that respiratory symptoms predominated would seem to make malaria, where positive tests have been seen in preliminary testing, a less likely explanation. Malnutrition seems to be a significant risk factor.

WRIS

Winter Respiratory Infection Season continues to mount with moderate level activity in the US driven primarily by RSV.

Epidemic trending (modeling data for predictions, from the same link as above) shows continued growth for covid ...

.... and especially for influenza.

It's still not too late for flu vaccine. Expect a surge soon if not already started in your area.

RSV Vaccine Conundrum

I was glued to my screen for much of last Thursday's FDA VRBPAC meeting, with the majority of the session devoted to discussion of pediatric RSV vaccine progress, or lack thereof. As I've mentioned in previous posts, RSV vaccine development for children was set back by a tragic trial in the 1960s where vaccine-associated enhanced respiratory disease (VAERD) resulted in 2 deaths of children who received vaccine and then subsequently were infected with wild-type RSV the following season. Through many scientific advances over the years, researchers determined that the cause of this enhanced disease was immunologic in nature, related to the vaccine causing recipients to develop a strong cellular immune response involving a specific class of T cells (Th2). This finding even influenced development of the mRNA covid vaccines which deliberately avoided this and ensured a Th1-predominant response and very safe vaccines.

Unfortunately, recent experiences in trials for Moderna RSV vaccines suggested that VAERD might be occurring in children under 2 years of age. Moderna was developing 2 mRNA RSV vaccines, 1 for RSV alone and another that also incorporated a human metapneumovirus vaccine. They were enrolling children in a phase 1 study this summer when the concerning signal arose. I am including slides from the FDA presentation. Here's the study overview and timeline of events this summer, from slide numbers 11 and 12.

I included the above to demonstrate that the safety constraints incorporated into the study worked exactly as intended. Enrollment was paused pending evaluation of the events, which is still ongoing. The imbalance between vaccine and placebo recipients is highlighted below:

Note the small number of children in the study, appropriate and typical for phase 1 trials. However, that makes analysis more difficult. I'll cut to the conundrum chase. Preliminary immunologic studies from patients in the Moderna trials suggest that the vaccine, as planned, produced Th1-predominant responses, and that the mechanism of the possible VAERD events is not due to Th2-primed cells. Furthermore, other immunologic data don't provide another plausible information for why this happened.

Of course, with so few trial subjects, it's possible that this imbalance of severe disease could be due to chance alone. Regardless, Moderna officials announced that they would be abandoning the mRNA RSV vaccine development but will continue to follow all the children already enrolled in their studies and perform further immunologic and other testing.

So, where does that leave us with RSV prevention? This took up much of the VRBPAC's discussion time. It's important to understand that the Moderna RSV vaccines were part of a larger group of pediatric RSV vaccines in various stages of development, 26 in all. Fifteen of these are live attenuated vaccines, and it should be noted that live-attenuated vaccines have never been shown to result in VAERD, with extensive validation for why that hasn't occurred. (I might add that your dog's kennel cough vaccine might contain one of these. Although Bordetella bronchiseptica is the most recognized cause of kennel cough, canine adenovirus - 2 and parainfluenza virus 5 are other common causes of kennel cough and also have been included in some intranasal dog vaccines for decades. Presumably most of us have been exposed to our dogs' live attenuated vaccine PIV5 strain many times, yet no human VAERD involving parainfluenza virus has ever been described.)

It is likely that future pediatric RSV trials will need to be judged on an even more individual basis, perhaps with separate constructs governing the various platform differences (live attenuated, viral-vectored, mRNA if anyone moves forward with this, and subunit protein) as well as mode of delivery - mucosal (intranasal) versus systemic by injection. In the meantime, we know that maternal immunization is highly effective, as is the infant monoclonal antibody nirsevimab. In that light, we also need development of newer monoclonal antibody products in case nirsevimab resistance appears, as well as better maternal vaccines that won't be so limited in timing of administration during pregnancy. Work is ongoing in all of these venues.

Conundrum

Of course I had to look into the origins of the word, but it turns out there is a lot of disagreement about this. I was most delighted to see the word explained as a "burlesque imitation of scholastic Latin." I was unaware that it was the title of a Jethro Tull instrumental song (I'm not much of a Tull fan) and an episode of Star Trek: The Next Generation (I am a fan, but don't remember the episode).

Have a great week, and don't forgot to offer flu and covid vaccines to your patients and families.

Published on Leave a comment on My Hebdomadal Habit

One of the many reasons I love to read is to discover new words to add to my vocabulary. Reading Colin Dexter reminds me of the need to keep a dictionary close by.

WRIS

The US Winter Respiratory Infection Season hasn't started yet; activity is low to minimal everywhere.

Note that the map above is a new twist from CDC: rather than "Influenza-Like Illness" activity, this reflects all acute respiratory illness by not requiring fever in the definition. So, it probably picks up more of all those other respiratory viruses out there. For the 2 graphs below, just use the same link above and scroll down.

Percentage of ED visits due to the "big 3" viruses is minimal, with covid dropping dramatically.

Since I'm trying to figure out the best timing for my own flu shot, I looked at influenza A wastewater tracking:

Only Rhode Island makes it to moderate activity, all the others with data are minimal or low. Probably the key part of the map above is the number of hatched/limited coverage states. For example, New York flu A wastewater activity only includes Albany and Rochester, not much help to the New York City folks.

Given the WRIS lull, clinicians might be interested in a recent CDC overview of covid and flu management. I couldn't log on to the live presentation but reviewed the slides and took the test for (free) CME credit. The presentation was well done, I recommend it as a good review.

Forbear the Bear (Meat)

Not that long ago (5/24/24 post) I relayed a CDC report about a 2022 trichinellosis outbreak linked to frozen Canadian bear meat. Less than 5 months later, CDC is telling us about another one, this time from 2023 at a single "feast" in North Carolina. It doesn't have as much detail as the earlier report, we don't know much about the food preparation methods and none of the ill persons returned for confirmatory lab testing. It certainly sounds like trichinellosis, however; in addition to a nonspecific febrile illness, 9 of the 10 probable cases reported facial swelling which for me is a T. spiralis infection clue.

I visited a number of wild game/hunting sites to see what advice consumers of bear meat might see. Most sites correctly cautioned hunters to cook bear meat to at least 165 F internal temperature, but a few did not. Also, many mentioned other wild game meats that taste better than bear meat. I won't be ordering bear meat anytime soon, but if you are drawn to the experience check out the CDC web site or this advice from Massachusetts that also includes recipes!

Travel to Rwanda?

Last week I mentioned the Marburg virus outbreak in Rwanda, and this past week CDC upgraded a travel alert for the area which has caused quite a kerfuffle. Rwanda now has a CDC level 3 travel alert status, meaning that nonessential travel to the area should be reconsidered. Three days after the CDC advisory, WHO pushed back. WHO believes that travel restrictions will be ineffective in controlling the outbreak plus may prove harmful to local economies and serve as a disincentive for sharing of public health data from those countries, harming control efforts. These are valid concerns; choosing the proper course of action probably requires something approaching the wisdom of Solomon.

Also, an experimental Marburg vaccine has made its way to Rwanda, now primarily being used and studied in health care providers who form the bulk of new cases, plus other high risk individuals. This study is of extreme importance, and I'm hopeful that we'll see good data eventually.

OED

For a brief moment in my past, I longed to have a complete print version of the Oxford English Dictionary at my elbow. It was short-lived: the standard version comes in 20 volumes and now lists for $1000+. A bargain is the "compact" version at about half that price; it is a "photo reduction" of the original, with 9 pages of the original on each single page. It comes with its own magnifying glass.

It's a lot easier to just look at the online OED to find out that hebdomadal means "weekly." I also learned that it's not commonly used, fewer than 0.01 occurrences per million words in modern written English. Maybe I've now bumped that up to 0.02.

Dexter's Inspector Morse character, in his second installment entitled Last Seen Wearing, mentions his "regular hebdomadal debate" when faced with his weekly dilemma of whether to purchase the more cultured Sunday Times versus the coarse News of the World at the newsstand. I can see parallels to my own cultural preferences in literature, music, and art. However, the hebdomadal part of my habits clearly is this blog. Any further resemblance to Inspector Morse ends here though; he is a true, albeit fictional, polymath who happens to be a detective. I am a real-life physician who happens to have diverse interests, like most of us.

Unless otherwise indicated, the content and opinions expressed on this web site are those of the author(s). They are not endorsed by and do not necessarily reflect the views of the George Washington University.
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