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We've had a slow week of infectious diseases events, but that hasn't slowed down the chatter and noise. I've tried to distill out the more important topics this week.

The Covid Front

Even though US tracking systems have been greatly dismantled in many states, I can still safely say we are in a lull. Naturally, thoughts turn to predicting the next surge and how to mitigate it.

I mentioned in my May 5 post that the FDA's Vaccines and Related Biological Products Advisory Committee meeting to decide on composition of the next iteration of covid vaccine would be held on May 16 and likely would make the same decision as the WHO already has, using the JN.1 variant. However, they suddenly postponed this meeting to June 5. FDA didn't offer an explanation for the postponement, but the last-minute change leads me to suspect that they wanted a little more time to think about newer variants with possible significant differences in immune-escape properties. Here's a deeper dive into that.

As you can see in this latest CDC variant report, the dark purple JN.1 proportion is decreasing, with KP.1 and KP.2 starting to expand. Both of those are in the JN. 1 lineage:

All of the JN and KP variants are informally called FLiRT variants, an easier shorthand than trying to remember all the letters and numbers. It stands for amino acid substitutions, in this case phenylalanine (F) substituted for leucine (L) in the 456 position (F456L) and arginine (R) to threonine (T) in the 346 position (R346T) in the spike protein genomic code. These 2 mutations are in antibody binding sites that neutralize the virus, and the mutations make SARS-CoV-2 less vulnerable to vaccine- and infection-acquired antibodies. A JN.1-derived vaccine likely would offer some protection, but perhaps by the June meeting we'll know a bit more about all of this. If they do recommend using KP.2 instead of JN.1 for example, I don't think there would be a significant delay in mRNA vaccine production by Pfizer and Moderna, but it might cause problems for other vaccine platforms such as the one used by Novavax, the other approved vaccine in the US which is an adjuvanted protein subunit vaccine. I'll be watching as much of the June 5 meeting as I can.

HPAI

Now we have a grand total of 2 people in the US infected this year with Highly Pathogenic Avian Influenza, along with a lot of cattle and other animals; a recent MMWR provides details. The new, improved CDC website has lots of helpful links. The second case, in Michigan, was similar to the first human case of A H5N1 infection in Texas - very mild illness with conjunctivitis as the primary symptom. This strikes me as very unusual for evolving epidemics in that usually the more severe cases are identified first because they are more likely to come to medical attention. Both of these cases were identified through surveillance of dairy workers which suggests to me that currently HPAI in humans is a very mild infection, possibly with high rates of asymptomatic infection. This is a good thing generally, but also problematic for tracking infection rates. The MMWR reports only 350 exposed dairy workers are being followed, a very small number. Ideally we'd have more tracking of cattle and dairy workers, regardless of illness or exposure to infected animals. Getting cooperation from dairy farms will be difficult, we're talking about livelihoods in an industry where a shutdown for a cow outbreak could send someone into bankruptcy.

I'm watching multiple feeds to keep up with all of this. A report in NEJM last week was encouraging - heat inactivation of spiked milk samples significantly lowered infectivity in mice fed the milk.

Also in the good news department, USDA reported preliminary findings on HPAI detection in muscle tissue of culled dairy cows. 95 of 96 samples tested so far were negative by PCR. Note that these were condemned animals, none of the meat entered the food supply.

On the somewhat negative side, more cattle herds have been hit with the virus, according to USDA.

Poultry outbreaks also continue with Minnesota registering more detections last week. Note that backyard flocks are not immune to HPAI.

On a slightly related topic, I was disappointed but not surprised to learn that the World Health Assembly, the decision body for the WHO, removed a pandemic preparedness treaty that was to be discussed at their meeting starting May 27. It appears that political considerations caused the cancellation; much misinformation is circulating, especially in the US. The treaty would help countries design programs for pandemic preparedness and in no way allows the WHO to control countries' own public health programs as claimed by some sources.

Potpourri

A scattering of reports might be interesting for readers. First, beware of undercooked bear meat. Six out of eight people who consumed undercooked, previously frozen black bear meat developed trichinellosis. Freezing doesn't kill Trichinella parasites. Beware the (undercooked) bear.

CDC released a Health Advisory Network alert for meningococcal disease in Saudi Arabia, although this is pretty much routine for this time of year during religious pilgrimage season. Travelers to the region should be immunized for meningococcal disease, which is more easily transmitted in the crowded situations during Islamic pilgrimages to Mecca.

Speaking of Noise

I'm pretty sure I've never mentioned this in the blog, probably because I'm so embarrassed, but I'm a 2-time harmonica school dropout. This last exit was due to a combination of my inability to master bending notes on the diatonic harmonica and the fact that my dog runs away from me every time when she hears my mellifluous tones. I've now solved the second problem by clearing a practice space in my trash-heap of a basement where the dog can't hear me, but bending will still be a challenge. It's a technique to hit notes that are in between standard notes; there are maybe hundreds of online instruction sites for how to form your mouth to do this, but basically it's just trial and error and takes several months for most people.

Graphic courtesy of Luke.

Maybe by announcing my intentions I'll be shamed into pulling it together this time and can return to harmonica school. I can't promise to report on my progress, especially if I have none!

Well of course there is, that's why I try to sprinkle my weekly posts with comments on bird feeders, squirrels, novels I've been reading, and other escapades. This past week I happened upon a former colleague of mine who has taken this to new levels, much to my enjoyment.

We seem to be free of serious infectious diseases drama in the past week, unless you are a dairy cow.

Avian Flu

Initially only previewed in news reports and even now lacking details, one thing is clear: influenza A H5N1 infection in US dairy cows is much more widespread than previously revealed. We were surprised by this because asymptomatic infection is common and cow testing was only being performed in symptomatic animals. (This is reminiscent of the early days of covid!) The FDA and Department of Agriculture both report finding positive avian flu PCR tests in 1 out of 5 samples of pasteurized milk tested, although I can't find details about the total numbers and the geographic distribution of milk samples tested.

Of course, a positive PCR merely means that nucleic acid has been detected. It is highly likely that pasteurization inactivates H5N1 virus, and preliminary reports from FDA suggest this is true. Again, details are not available, but certainly no cause for panic about drinking pasteurized milk.

The take-home messages are clear: 1) H5N1 infection is highly prevalent in US dairy cow herds if 20% of all milk samples are PCR positive; 2) there is even more reason now to avoid ingestion of unpasteurized dairy products; and 3) USDA, FDA, and CDC are performing poorly in providing transparency and detailed evidence to the public. They say they are working on this, let's hope we see the fruits of that labor in the coming few weeks.

And, to give our federal agencies some credit, CDC has a spiffed-up web site for avian flu now, with weekly updates. Here's a quick view for the week ending April 20:

Note that this site deals only with human disease. If you want to get more on dairy cattle, you'll need to go to the USDA site. Here you can realize how geographically widespread the situation is.

USDA now has new guidelines for testing dairy cattle being transported interstate. Perhaps testing needs to be expanded beyond just interstate transport.

Covid Calm

Covid activity continues to fall, and weekly deaths now appear to be consistently less than 1000 even considering there is significant reporting delay for covid deaths. The vast majority are in the elderly.

Two new studies appeared highlighting covid vaccine side effects in children. One was a prospective cohort study utilizing insurance databases that likely carried some risk of classification errors because the authors did not perform any medical records review for verification. The study confirmed the known risks for myocarditis or pericarditis for ages 12 - 17 years with the Pfizer vaccine. Also, they found a possible safety signal for seizure occurring following both Pfizer and Moderna vaccination in 2 - 4 or 5 year-old children. This is pretty iffy; as they explained in the body of the text, it may simply be an artifact of how they defined the baseline seizure rate as a comparison number. This is worthy of further study, but in my opinion not something that should be put on the list of definite side effects yet.

The other study was a massive (3.9 million children) look at covid cases in California from 4/1/20 through 2/27/23, again using an administrative database. The article has too many explanatory graphs to show here, but the bottom line from the authors' predictive models suggests that vaccination prevented about 146,000 covid cases in 12 - 15 year-olds, 230,000 cases in 5 - 11 year-olds, and 168 hospitalizations in 6 - 59 month-olds. The authors did not find any association of vaccination with numbers of cases in the youngest age group, possibly because the numbers of vaccinated children were too small during the study period.

Our friends across the pond reported on various covid features from this past winter, November 2023 through March 2024. Results are based on self-reported data from a longitudinal survey study. Here are the main points:

  • An estimated 3.3% (2 million) of people living in private households in England and Scotland were experiencing self-reported long COVID (symptoms continuing for more than four weeks after a confirmed or suspected coronavirus (COVID-19) infection that were not explained by something else).
  • Long COVID symptoms adversely affected the day-to-day activities of 1.5 million people (74.7% of those with self-reported long COVID), with 381,000 (19.2% of those with self-reported long COVID) reporting that their ability to undertake their day-to-day activities had been "limited a lot".
  • Those in the youngest (aged 3 to 17 years) and oldest (65 years and over) age groups were the least likely to test positive for COVID-19 during the study period.
  • Those who have had a vaccination since September 2023 were less likely to test positive in the early waves of the study period (1 and 2); in later waves of the study period (3 and 4) there was no statistical difference.
  • Participants in the oldest and youngest age groups who did test positive in the study period were also less likely to report symptoms consistent with "influenza-like illness" compared with those in the middle age groups.

It's hard to find such recent data. I think this gives us a good peek at the future, assuming we don't have some major change in virus virulence or transmissibility.

Encouraging Progress in Malaria Prevention

I don't usually mention phase 2 trials because they are often much removed from clinical applicability and might change significantly once phase 3 trials are completed. This study is cause for optimism, so I'll break my custom here. Investigators in Mali performed the trial, part of which looked at 225 children randomized in equal numbers to a long-acting monoclonal antibody against Plasmodium falciparum with low dose, high dose, and placebo groups. Infection and clinical malaria was much less in the treatment groups.

The antibody is administered subcutaneously, a plus in resource-poor environments. If further studies confirm efficacy, this could save many lives.

Measles

No new cases were reported in the past week, good news though we know there will be more eventually. Also, I've been looking for more reliable assessments of worldwide activity and found another resource for Europe, the European Centre for Disease Control and Prevention. Updates appear only monthly. Here's what the most recent report, February, looked like:

Romania is the major hot spot, but note that many popular tourist destinations are represented. Here are current CDC recommendations that apply for all international travel:

Fiddlin' Will

By a happy occurrence in my web wanderings, I discovered a former colleague of mine was performing with his band, the Goldbug Revival, at a Salvadoran restaurant near my home. I crossed paths briefly with Will Sears when he was an infectious diseases fellow at NIH; he is now a medical officer at NIAID. However, in his "spare time," he is an accomplished musician. I was thrilled to see him on the fiddle and his wife Sarah singing lead at the band's first live performance and Sarah's first performance in front of a microphone ever. They were excellent!

See you next week. I'll be listening to some John Prine music in the meantime, waiting for Goldbug Revival's first album to drop. Prine was an early covid victim, dying in April 2020.

I finished a wonderful novel last week; among other things, it reminded me of the beauty, complexity, and destructive forces in nature, certainly applicable to infections, pathogens, and vectors of disease.

The past week saw more publications than I could cover in depth (or that readers could tolerate, probably), so I had to narrow things down even more than I usually do. If you're feeling particularly adventuresome, some of the topics I excluded pertain to a new phase I Chlamydia vaccine trial that could prove to be a breakthrough eventually, more advice on use of the new pentavalent meningococcal vaccine, an in vitro study suggesting nasal epithelial properties account for less severe covid disease in children, and a tularemia outbreak in Utah beavers. I also left out the growing Salmonella outbreak linked to organic basil, though I did alert one of my sons who often shops at a store featuring the tainted product. Here's what made the cut this week.

Respiratory Disease Transmission is Not Binary

Most things in biology and medicine aren't binary, even if we tend to reduce our thinking to that level to simplify things. For example, most lab tests aren't just positive or negative, even though they are reported that way. The cutoff between those two choices are made to maximize specificity and sensitivity of the tests, but they don't necessarily work for all circumstances.

The World Health Organization provided an important new proposal for changing our longstanding terminology for spread of respiratory infections as either droplet or aerosol (airborne). It's just not that simple, as SARS-CoV-2 painfully taught us. I found I couldn't improve on WHO's explanation of the complexity of pathogen transmission through the air, so here it is verbatim with some highlights in red that are mine:

The following descriptors and stages have been defined by this extensively discussed consultation
to characterize the transmission of pathogens through the air (under typical circumstances):

  • Individuals infected with a pathogen, during the infectious stage of the disease (the source), can generate particles containing the pathogen, along with water and respiratory secretions. Such particles are herein described as potentially ‘infectious particles’.
  • These potentially infectious particles are carried by expired airflow, exit the infectious person’s mouth/nose through breathing, talking, singing, spitting, coughing or sneezing and enter the surrounding air. From this point, these particles are known as ‘infectious respiratory particles’ or IRPs.
  • IRPs exist in a wide range of sizes (from sub-microns to millimetres in diameter). The emitted IRPs are exhaled as a puff cloud (travelling first independently from air currents and then dispersed and diluted further by background air movement in the room).
  • IRPs exist on a continuous spectrum of sizes, and no single cut off points should be applied to distinguish smaller from larger particles, this allows to move away from the dichotomy of previous terms known as ‘aerosols’ (generally smaller particles) and ‘droplets’ (generally larger particles).
  • Many environmental factors influence the way IRPs travel through air, such as ambient air temperature, velocity, humidity, sunlight (ultraviolet radiation), airflow distribution within a space, and many other factors, and whether they retain viability and infectivity upon reaching other individuals.

WHO still proposes a somewhat binary system of IRP spread, with "airborne transmission/inhalation" denoting pathogens which can spread at both short and longer distances, depending on various factors, versus "direct deposition," e.g. someone sneezes on you. It still may be confusing, but this is an important attempt to get past somewhat misleading advice such as a establishing a standard 6-foot distance between persons waiting in line.

Children and Adolescents Likely Still Benefit From Covid Vaccination

CDC has an update on covid vaccine effectiveness and durability, looking at the original monovalent vaccines over the time period from mid-December 2021 to late October 2023. Two doses of vaccine were 52% (95% CI 33%-66%) effective against hospitalization in the 5 - 18 year-old age group if vaccines were received no more than 4 months prior to hospitalization. From 4 to 12 months, protection against hospitalization waned significantly to 19% (95% CI 2%-32%). The report doesn't mention children less than 5 years of age, I suspect because vaccine authorization occurred later, numbers vaccinated are too small, and hospitalization was too uncommon to give reliable numbers.

Vaccine Adverse Events: New Numbers and a Terrific Interactive Web Site

The National Academies of Science, Engineering, and Medicine published new reports on adverse events from covid vaccines as well as an assessment of shoulder injuries from all vaccine administrations. The reports are excellent, but I fell in love with their web site. The NASEM group used levels of evidence to summarize current knowledge about various vaccine adverse events. The categories are evidence that a) establishes a causal relationship; b) favors acceptance of a causal relationship; c) inadequate to accept or reject a causal relationship; or d) favors rejection of a causal relationship. (Certainly this is far from a binary categorization!)

For covid vaccination they looked at six categories of adverse events: cardiac and vascular, female infertility, hearing conditions, immune-mediated events, neurologic events, and sudden deaths. The interactive web site allows you to pick and choose among various topics and subtopics and vaccines. Here's what the portion on myocarditis looks like:

Here's a look at acute biceps tendinopathy from vaccine administration in general:

You can also access the pdf version of the report (note it is a pre-publication proof, could contain some typos) to look at the summary and/or more details.

A Significant Change for Syphilis Screening From ACOG

I'm thrilled to see new recommendations for syphilis screening of pregnant people from the American College of Obstetricians and Gynecologists. I feel like my practice is a congenital syphilis quagmire right now. This updated recommendation gets away from the risk-based approach for screening which has always been a bit vague and clearly less useful with the resurgence of syphilis in the US. Now, every pregnant person should have syphilis testing 3 times: at the first prenatal visit, during the third trimester, and at birth. Previously a pregnant person with good prenatal care could escape with being screened only once early in pregnancy, a practice that would miss recent infection or infection acquired later in pregnancy. They also remind us that 40% of congenital syphilis occurs in infants whose mothers did not receive prenatal care; syphilis screening should be considered for pregnant people at every interaction with the healthcare system, such as emergency or urgent care visits.

Fake News From USDA?

Because of the avian flu concerns in the US, I've been trying for the first time to use alerts from the US Department of Agriculture on the status of avian influenza in wildlife and domesticated animals, including the recent importance of dairy animals. So far the alerts aren't telling me much, just clogging my in box with unhelpful information. So, I was a bit dismayed to see a recent NY Times article criticizing USDA transparency. Unfortunately the article requires a subscription, but it mentions an "obscure" USDA update (that I didn't receive) mentioning influenza A H5N1 further spreading among dairy cow herds and from there to poultry. More distressing to me is a claim in the Times article stating that asymptomatic infections have been discovered in a herd, but not yet reported by USDA; this is important since screening advice for dairy farmers currently is focused on symptoms in the cattle, with no screening of healthy-appearing cows. Perhaps USDA hasn't reported this asymptomatic infection possibility because it hasn't been verified, but one hopes they will be more transparent (and provide better updates) than they have so far. CDC learned a lot about public communication and transparency during the covid pandemic that should inform communications from USDA and other government agencies that we depend on.

Measles

Only 4 new cases reported in the last week, hoping we stay in this lull for a good while.

Elm Beetle Romance

That novel I finished recently was Daniel Mason's North Woods; it's had mixed reviews but I thoroughly enjoyed it. The author happens to be a psychiatrist, and this recent offering from him is an entertaining look at the happenings in a house in rural Massachusetts over several centuries. I had a great chuckle from a brief description of Dutch elm disease complete with a steamy sex scene involving elm bark beetles. Maybe I need to get out more.

Bird flu has been in the headlines, accompanied by the usual extremes of concern levels. The past few weeks reminded me of Alfred Hitchcock's 1963 movie "The Birds," especially a diner scene where an elderly (my age?) amateur ornithologist (Ethel Griffies as Mrs. Bundy) attempts to explain why the "brain pan" size of a crow or blackbird makes any organized attack on humans impossible. The discussion is interrupted by another customer declaring the end of the world, interspersed with background shouts of orders for blood marys and fried chicken with baked potatoes.

Before we get to bird, a few other items of note.

Dengue Update

Maybe things aren't quite as bad, with a downward trend now apparent in the Americas.

The bulk of this atypical seasonality increase is from the Andean and Southern Cone regions of South America. Brazil by far leads the way, and Argentina, Peru, and Paraguay are in a second tier by numbers of cases. Here's a numbers breakdown for last week and for the calendar year as a whole:

Don't Dismiss Covid

Yes, the current variants and immunity levels in the US seem to result mostly in mild disease and numbers continue to trend downward, but we are seeing well over a thousand deaths per month from covid in the US. It is still a devastating disease.

Measles Still Hanging Around

No outbreaks in new jurisdictions in the US in the past week; Illinois and Florida still account for most of the cases this calendar year.

Highly Pathogenic Avian Influenza (HPAI)

The name itself is pretty ominous, cue those eery bird sounds from the movie. The biggest event last week was the confirmation of a case of influenza A H5N1 infection in a man from Texas, almost certainly acquired from the dairy cows he worked with. He was treated with oseltamivir and apparently is doing well. CDC issued a health advisory through their Health Alert Network last week, including a lot of good advice and helpful links. People who are around birds or dairy animals should take care; this includes those with backyard chicken flocks. The public health messaging has been pretty consistent: no cause for alarm, and certainly no reason to avoid dairy products or eggs at your local store (assuming the dairy products are pasteurized). FDA has a great Q&A page on this.

Note however that we have pockets of these viruses throughout the US, including in wild mammals.

We can be reassured that all of these strains are being tracked and sequenced worldwide through the Global Influenza Surveillance & Response System (GSAID). Scroll down at that link to watch an animation of the geographic spread of influenza A H5Nx viruses worldwide over the past few decades.

We have several antiviral therapies available, and vaccine prototypes are ready to enter mass production if necessary. So far, none of these strains seem well adapted for human-to-human spread, but if that happened it would be a major event that would cause much more concern. I'm also watching to see if this appears in pig populations, since swine flu viruses have been seen in the past to foreshadow human spread. Pigs have similar flu viral receptors to humans, so spread in pigs can be seen prior to a jump to humans. Thankfully, many of the events that facilitate spread among different animal species also are associated with lower virulence, so clinical impact is minimal.

Don't Look Up (Without Your Eclipse Glasses)

Yes, I know it's yet another movie. Just be careful with tomorrow's eclipse.