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Summer is supposed to be the slowest season in my line of work, but it doesn't seem like it. I've had trouble keeping up with everything, including some old news that I just found out about today. Maurice Williams died on August 5. If that name doesn't ring a bell, stay tuned. Here's what's up for this last post of the summer.

Mpox

It looks like we can add Gabon to the list of countries with exported mpox, this in a 30-year-old man who had stayed in Uganda for 2 weeks. The notice doesn't state whether or not this is clade I, but given that it appears to have been acquired in Uganda there is a good chance that it is. The latest WHO news was posted on August 22, the same day we heard from the CDC about the US response.

By no means is this the next pandemic, but we are seeing global spread of the clade I strain via travelers. Most important is ensuring affected African countries receive adequate vaccine supplies soon. In the US, persons in high risk groups also should be vaccinated.

Measles Check-In

Oregon is the latest state in the measles outbreak spotlight. Nationally the cases are percolating along at a steady rate.

West Nile Virus

In my post last July 28, I was halfway kidding about waiting for symptoms of West Nile virus after all my mosquito bites. West Nile is in "full swing" in Europe currently. Now I see in today's Washington Post that Tony Fauci is back home after a 6-day hospitalization for West Nile infection. Although he is 83 years of age, that's a long hospitalization and I hope he didn't have serious neurologic or other complications. I wish him a speedy recovery.

A little trivia piece I discovered years ago, did you know West Nile virus was tried as a cancer treatment in the early 1950's? Research on using flaviviruses as oncolytic agents continues. Unfortunately the lead investigator of that 50's study is mostly remembered for a serious ethical breach, injecting tumor cells into prisoners to study tumor immunology.

Timing is Everything

I have a complicated plan for how I'm going to time when I get my flu and covid vaccines in the coming weeks, based on travel plans and guessing about peak flu season. At my age, waning immunity following vaccination could be clinically significant.

This brings me to an interesting study in the BMJ trying to define optimal timing for influenza vaccination in young children. It utilized data from an administrative database in the US for timing of vaccination of over 800,000 children ages 2-5 years during several flu seasons. Bottom line, it looked like October was optimal. I wouldn't necessarily alter plans based on this study; every flu season has slightly different timing. It's probably a better plan to just vaccinate when you can, whether it be at regular checkups or flu vaccine events on evenings and weekends.

Holding My Breath on Polio

I'm still hoping polio doesn't break loose in Gaza, but I'd be more hopeful if vaccine could be distributed there. WHO has full plans in place to distribute the relatively new novel oral polio vaccine type 2 (nOPV2) to about 640,000 children under 10 years of age in 2 campaigns separated by a month. Wastewater monitoring suggests this is the strain that caused the case recently detected in a child in Gaza; we're still waiting for confirmation from a regional lab in Lebanon. Now we just need an effective ceasefire to allow this and other humanitarian aid to be implemented.

Covid

The big news was the not surprising FDA approval and emergency use authorization of the KP.2-based mRNA vaccines from Pfizer and Moderna. Novavax approval is still pending due to a longer manufacturing process. As I've said many times, if one looks at the level of individuals, it's pretty clear that vaccination benefits outweigh risks for every age group. New interim recommendations are available from the CDC.

Here's a quick look at a few disease activity indicators over the past year:

Wastewater hasn't changed much nationally.

Regionally, only the Northeast seems to be rising, though still lower than most other regions.

We'll see what happens with covid (and measles) now that schools are starting back again.

In the midst of all this, we have a new study on long covid in children. It was a multicenter prospective cohort study of about 900 younger children and 4500 adolescents, most with covid infection but some not infected who served as controls. The report is loaded with data and complexities; I'm sure everyone in the field is looking it over closely.

It's tough to summarize the findings succinctly, but perhaps you can enlarge the figure below to see details. The darker color shades are the more prominent symptoms in each cluster. Clustering of types of symptoms varied between adolescents (12-17 years) and school-age children (6-11 years). I'm very happy to see this type of analysis; it is possible that different clusters have different pathogenetic mechanisms suggesting different treatment approaches. Clusters in the younger children were in the neurocognitive, pain, and GI domains, whereas loss of smell or taste, pain, and fatigue/malaise were highlighted for the adolescents.

This study won't change clinical practice immediately, but it is a major step forward in providing a framework to base treatment studies.

"No Good Songs Ever Came Out of the 1950s"

That probably inaccurate quote, heard when I switched my car's Sirius/XM to the 50's station, came from a musically-inclined and knowledgeable friend of mine. I'm pretty sure he uttered it just to get a rise out of me, which it did. IMHO, the 50's produced a lot of good songs and shouldn't be remembered just for some wacky West Nile virus studies.

The title of this week's post is a nod to Maurice Williams who wrote the song "Stay" in my birth year, 1953, but then put it on the shelf until he recorded it with the Zodiacs in 1959. It came out in 1960 and was a big hit at just 90 seconds in length. You may be more familiar with it from the 1977 cover with slightly altered lyrics by Jackson Browne, Rosemary Butler, and David Lindley (and the 9-minute mini-medley with "The Load Out") or from the 1987 movie "Dirty Dancing" that used the Williams original. Regardless of which of the couple dozen versions I listen to, this is one of those songs that always brings a smile to my face.

The title above is one of several great turns of phrase in the book I just finished reading, Edith Wharton's Age of Innocence. It refers to an episode where the protagonist was at a loss for words during a poignant encounter and presumably only later thought of something better to have said. I've been there.

Next Round for Covid Vaccine

The FDA's Vaccine and Related Biological Products Advisory Committee finally had their meeting last week; it had been postponed to give a little more time to see which way the new SARS-CoV-2 variants were headed. I was able to listen in on most of the meeting and have reviewed all the documents. The vote was unanimous to choose a monovalent JN.1-based vaccine for the next iteration, no surprise and in agreement with the recent WHO decision I discussed recently. (For those interested, there is quite a bit of international collaboration on these types of decisions. See the ICMRA posting about covid vaccines.) Still, there were some interesting updates on covid in general. I'll try to distill this down into the main takeaways.

The Latest on Epidemiology (from Thornburg FDA presentation)

Current circulation of SARS-CoV-2 is relatively low. Although our reporting is not as reliable these days, looking just at percentage of positive covid tests in orange you can see we are in a lull now, though perhaps with a hint of an uptick. This is pretty similar to last summer when we saw a bit of a surge in summer into fall and winter. SARS-CoV-2 still has not come around to a winter seasonality seen with other coronaviruses of with influenza, making predictions for surges and vaccine composition very tough.

JN.1 lineages replaced XBB.1.5 lineages during winter 2023-2024. I like the depiction below because it's looking at normalized numbers of positive tests rather than a percentage of positive tests due to different variants. This gives a better appreciation of numbers of cases and shows that we are still talking about relatively low numbers compared to 2022.

Here's a closeup of the most recent part of the above slide showing that KP.2-like, KP.3, and other JN.1 derivatives are starting to take over, though still all at very low numbers.

The recent subvariants have very few differences from other JN.1-derived strains and antigenically are very similar. This has important meaning for vaccine choice - should it be the original JN.1 variant or one of these newer KP.2 or KP.3 type subvariants, currently at extremely low numbers? Look at the last 2 rows in the table below, showing that these newer subvariants have very few mutation differences from the earlier JN.1-like variants.

In a totally new and as yet unpublished CDC analysis, severity of JN.1 infections does not appear to be worse than earlier lineages. The trend was towards milder illness, though not statistically significantly different. Note these numbers are just for adults.

Vaccine Effectiveness in Children (from Link-Gelles FDA presentation)

This it tough to estimate because children generally have milder disease, plus so few children are vaccinated. Adult data is pretty favorable for VE; SGT failure is a faster method of testing and correlates will with JN.1 lineage strains. 2023-2024 VE drops a little with these strains compared to effectiveness against XBB lineage strains.

On the pediatric side, it's important to remember that the vast majority of US children have been infected with SARS-CoV-2 at some time in their lives - this has been apparent since late 2022.

So, it's important to determine any VE now in light of prior infection and vaccination. We can't rely on older estimates. Here's the best and latest estimates for VE in children who received vaccine in the past year. Confidence intervals are relatively wide, reflecting the small numbers able to be studied, but do show benefit in prevention of ED or urgent care use. VE wanes with time after vaccination as it does with all age groups, but there is clear benefit for covid vaccination of children.

David Wentworth, representing WHO, delivered a wonderful explanation of the complexities in choosing among current subvariants for vaccine inclusion. He had this great quote: "... antigenic evolution just speeds up waning immunity." The variant evolution we're seeing now is parallel, i.e. lots of different subvariants evolving on their own, in parallel, rather than one subvariant evolving into another, and then into another, etc. Parallel evolution is what XBB lineages did previously, and we're seeing it now in the JN.1 groups. The slide below demonstrates this process with a timeline on the X axis.

The dilemma in choosing composition of the next vaccine is that no one knows which way the very new subvariants will evolve in terms of antigenic similarity to earlier JN.1 strains. Currently, KP.2, KP.3, and JN.1.23 are within what is thought to be close proximity to JN.1 in terms of antigenic similarity and therefore a vaccine based on any of those likely will have cross-reactivity with one another, enough to provide protection. However, as illustrated by the arrows, it just isn't known how the offspring of the newer subvariants will evolve - will it be farther away from JN.1 and each other, or will it remain relatively stable?

No one can predict what next fall's or winter's subvariants will look like. Once they appear, new lab testing would need to be done, ideally using human serum containing antibody to the newer strains, which Wentworth stated would take about a month to produce. So, it's not something that can be turned around quickly.

Also, it bears mentioning that virtually all of the immunity studies involve neutralizing antibody. Antibody does correlate well with VE, but T-cell immunity also is important. We don't see as much data about this arm of the immune system because the studies are more difficult.

All 3 US vaccine manufacturers, Moderna, Pfizer, and Novavax, presented their new data at the meeting. They are developing and testing new vaccines "at risk," meaning the companies are making vaccines without funding currently, risking their own research and development dollars, hoping whatever they are working on will be recommended for the next covid vaccine rounds and allow them to recoup their investment. Moderna and Pfizer have both developed JN.1- and KP.2-based mRNA vaccines. Novavax, the adjuvanted protein-based vaccine, only developed a JN.1-based vaccine. The protein vaccine takes much longer to construct than do mRNA vaccines, about 6 months to get good data in all. So, if a KP.2 or other vaccine were recommended, Novavax would need to start over and wouldn't be ready until about December.

I don't usually like to use pharma slides to illustrate points, but this one from Pfizer isn't biased in favor of their product and I think nicely shows the current situation, including how closely related the newer subvariants are to JN.1.

In the discussion after the vote to have a monovalent JN.1-based vaccine, which could mean one based on KP.2, the majority of the group felt that using the JN.1 variant rather than KP.2 or another subvariant was the best route, both to allow Novavax to be ready this fall but also not to take a chance that fall and winter predominant subvariants might be more antigenically removed from KP.2 antigenically. All in all I felt this was the right choice, though I probably wouldn't have let Novavax's problems affect the decision; very few US residents have received Novavax in the past, though it is nice to have an alternative to mRNA vaccines available.

On June 7 the FDA formally recommended sticking with the JN.1 strain for this next vaccine round. Next step with be the CDC's Advisory Council on Immunization Practices meeting the end of this month, where the official seal of approval will be issued. I'm sure Moderna, Pfizer, and Novavax already are ramping up production.

NASEM Long Covid Report Available

Long covid remains a quagmire, lots of different symptoms, many of which are vague, and still no definite light shed on diagnosis and treatment of what is likely a heterogenous group of conditions requiring different approaches. The National Academies of Science, Engineering, and Medicine published their full report, available free online. I haven't gotten through all of it, it's pretty long, but it is of interest to those practitioners who see these patients. Most of the evidence is from adults, but it appears that pediatric patients tend to have a better prognosis, especially if improvements are occurring in the first year after onset. Note that a positive covid test is not required for diagnosis testing may not have been done at the time of the triggering infection and antigen or PCR tests will have reverted to negative by the time a long covid diagnosis is considered.

Doxycycline for Post-Exposure Prophylaxis of STIs

The official guidelines appeared this past week, although the gist of the recommendations had been floated previously. Particularly high risk groups are gay, bisexual, and other men who have sex with men and transgender women. The summary is very helpful for practitioners who may want to print out and post Box 1 and Box 2 in their workspaces. Note that the recommendations apply just to those high risk groups.

Summer Bugs!

Bugs in the sense of both insects and microbes. We now have more details about a new rickettsial agent, termed species C6269, that caused a Rocky Mountain Spotted Fever-like illness in 2 individuals in northern California last summer. Both had severe disease, were hospitalized and treated with doxycycline, and survived. As always, keep RMSF and other tick-borne diseases in mind during our warm months.

Speaking of bugs, our dog came down with a skin abscess, expertly debrided by her veterinarian. She is now enjoying chewable amoxicillin/clavulanate but is less thrilled with her "cone of shame." The vet had another bug concern, however. She didn't want the dog to spend much time outside - apparently it is also maggot season, and they love open dog wounds. The vet doesn't know I'm an ID doctor, and I was trying to come up with some clever comment on maggots but failed at that moment - belated eloquence of the inarticulate!

Courtesy of Wikipedia. Hope you aren't eating as you read this.

It was a busy week for infectious diseases, not in the sense of more outbreaks but rather more epidemiologic and vaccine data that point to better health for the future.

The big topic of the week was the Advisory Council on Immunization Practices regular February 2-day meeting. In retrospect, pediatric healthcare providers won't have any major new recommendations to work with; those are likely coming following the next meeting the end of June. I wasn't able to view as much of the meeting as I had hoped, patient care interfered a bit, but I did review all the presentations for those that I missed hearing live. Let's dive in.

ACIP

The Council discussed 9 different topics, but only 3 involved voting: COVID-19 vaccines (vote in favor of a spring vaccine for some high-risk people), Chikungunya vaccine (vote for use in some US adult travelers and in laboratory workers), Td vaccine availability for those with contraindications to receiving pertussis vaccine (discussion followed by a vote regarding the Vaccines for Children progam), influenza vaccines, polio vaccines, RSV vaccines for adults, meningococcal vaccines, pneumococcal vaccines, and the new Vaxelis combined product for diphtheria, tetanus, pertussis, polio, Hib, and hepatitis B. I'll expand on just a few of these topics. (Note all of the graphs/figures below are from the ACIP web site presentation slide link for the February meeting.)

RSV

We saw the most up-to-date representation of RSV epidemiology, showing that the epidemic curve for this year looks a lot like prepandemic years (see last presentation in RSV session).

A good part of the discussion centered on risk of Guillain-Barre syndrome following vaccine, compared to risks of GBS in the baseline population. Both are rare events, but I think at this point it is reasonable to conclude that GBS is a rare risk of RSV vaccination, though not enough to outweigh benefits for high risk populations.

A quick look at the benefits versus GBS risks for adults > 60 years of age (Melgar presentation from RSV session):

Note risks might vary with vaccine type - hard to know with rare events and large confidence intervals, plus both in the ballpark of background GBS numbers.

Influenza

This session was interesting for me to see a preliminary assessment of vaccine effectiveness for the 2023-2024 flu season. I'll just show you an overview of VE in the pediatric population; note that multiple methodologies are used to measure VE. (See slides from Frutos presentation in the influenza section.)

This is good VE for flu, certainly the CDC and WHO were on track for choosing the best combination of strains for this season. Look for the vote for next season's vaccine composition in June.

Meningococcal Vaccines

The focus of the discussion was how best to incorporate meningococcal B vaccine now that we have an approved combination vaccine containing this serogroup. Here are the main options discussed, from the 1st Schillie presentation:

The issues are complex, primarily due to 3 factors. First, meningococcal group B infections are extremely rare; traditional cost-effectiveness models show that meningococcal B vaccination in the US is by far the most expensive vaccine; very few cases are prevented due to the rarity of infection. Second, vaccination at age 11-12 risks significant waning of immunity by the age for peak meningococcal disease in adolescents; it might make sense to move the first dose to a later age. (The main argument against this is the confusion caused by eliminating the long-standing practice for vaccination at age 11-12, perhaps lowering overall vaccine acceptance.) Third, it is clear that not all meningococcal disease risk in adolescents is equal: college attendance is prime, but there are other behavioral risk factors (1st Schillie presentation):

The discussion was mainly to hear input from all stakeholders and then go back to the drawing board. Expect a vote on this at the June meeting - it will greatly impact your summer vaccine guidance for adolescents and young adults.

COVID Vacines

This section of the meetings seemed to garner the most publicity. Of course most of the results presented dealt with adults, given the relatively lower risk for bad outcomes in children plus low rates of vaccinations. Most helpful I thought were the discussions about covid VE in recent months looking at the fall monovalent vaccine.

These are great numbers. Also mentioned was the fact that waning of efficacy hasn't been seen yet, but that could just be a result of not having enough time to pass since the fall vaccine. Other good news is that in vitro studies suggest that the current monovalent vaccine is likely to protect against newer variants.

The official recommendations from CDC now state

Special situation for people ages 65 years and older: People ages 65 years and older should receive 1 additional dose of any updated (2023–2024 Formula) COVID-19 vaccine (i.e., Moderna, Novavax, Pfizer-BioNTech) at least 4 months following the previous dose of updated (2023–2024 Formula) COVID-19 vaccine. For initial vaccination with Novavax COVID-19 Vaccine, the 2-dose series should be completed before administration of the additional dose.

That "should" wording was the subject of much debate, finally choosing this wording more for simplicity of recommendations. The gnashing of teeth came about for a good reason - people in the lower end of this age population who do not have underlying risk factors will have less benefit from a spring vaccine because rates of bad outcomes in the post-pandemic period are lower.

Recommendations for younger people with moderate or severe immunocompromise have slightly different wording:

  • People ages 1264 years who are moderately or severely immunocompromised may receive 1 additional dose of any updated (2023–2024 Formula) COVID-19 vaccine (i.e., Moderna, Novavax, Pfizer-BioNTech) at least 2 months after the last dose of updated (2023–2024 Formula) COVID-19 vaccine indicated in Table 2. Further additional doses may be administered, informed by the clinical judgement of a healthcare provider and personal preference and circumstances. Any further additional doses should be administered at least 2 months after the last updated (2023–2024 Formula) COVID-19 vaccine dose.
  • People ages 65 years and older who are moderately or severely immunocompromised should receive 1 additional dose of any updated (2023–2024 Formula) COVID-19 vaccine (i.e., Moderna, Novavax, Pfizer-BioNTech) at least 2 months after the last dose of updated (2023–2024 Formula) vaccine indicated in Table 2. Further additional doses may be administered, informed by the clinical judgement of a healthcare provider and personal preference and circumstances. Any further additional doses should be administered at least 2 months after the last updated (2023–2024 Formula) COVID-19 vaccine dose.
  • For all age groups, the dosage for the additional doses is as follows: Moderna, 0.5 mL/50 ug; Novavax, 0.5 mL/5 ug rS protein and 50 ug Matrix-M adjuvant; Pfizer-BioNTech, 0.3 mL/30 ug.

As an aside and not receiving much media attention, a new report showed that vaccine mandates didn't help and probably hurt. States with vaccine mandates didn't have higher covid vaccination rates and actually had lower covid booster uptake and flu vaccination rates. Yikes!

Nipah Virus

Never heard of it, or hard-pressed to find facts at the tip of your tongue? Most providers in the US don't need to know much about this bat-borne virus, but if you have any patients planning a trip to Bangladesh you may want to advise them not to consume raw date palm sap (not on my list of delicacies so far) and to stay away from pigs.

NiV gets its name from the village of Sugai Nipah in Malaysia, site of a 1999 outbreak highlighted by cases of encephalitis in pig farmers. Outbreaks typically occur in Bangladesh and India. Now, the World Health Organization reports that 2 individuals, including a 3-year-old girl, have died from the infection after consuming raw date palm sap. The sap likely was contaminated with fruit bat droppings laced with NiV. In addition to signs and symptoms of encephalitis, typical findings are those of nonspecific febrile illness. Diagnosis is difficult until/unless encephalitis findings appear. It's a relatively uncommon infection even in Bangladesh, but mortality is high.

Good Attitudes

It's a sign of our times that I was pleasantly surprised to see a vaccine attitude survey with good news. Investigators from RAND corporation, University of Iowa, and CDC performed an online survey of 1351 parents to assess their willingness to have their children 5-18 years of age receive a vaccine to prevent Lyme disease. About two-thirds of parents definitely or probably would vaccinate their children. The boldface numbers below show statistically significant predictors of willingness to have their children receive Lyme vaccine, with willingness of the parent to receive the vaccine the strongest predictor.

In case you were wondering, for the purposes of this survey the high incidence states were Connecticut, Delaware, Maine, Maryland, Massachusetts, Minnesota, New Hampshire, New Jersey, New York, Pennsylvania, Rhode Island, Vermont, Virginia, Washington D.C. (yes, I don't need to be reminded it's not a state), West Virginia, and Wisconsin. They also looked at states characterized as "emerging" Lyme disease states (Iowa, Ohio, Illinois, Indiana, Michigan, North Carolina), but this group had a slightly lower rate of willingness than in high incidence states. Lyme vaccine trials in the pediatric and adult populations are ongoing, so don't be surprised if parents and children have this option in the next year or so.

Speaking of attitudes, take a look at AAP's new guidance for improving vaccine communication and uptake. It has an excellent literature review and describes various strategies that pediatric healthcare providers can use to improve vaccine acceptance. It is still true that different studies sometimes have reported different conclusions on how best to discuss vaccine hesitancy with parents, likely because it is very difficult to design studies that deal with such subjective issues in a uniform manner.

WRIS

Winter respiratory infection season is still chugging along, mostly due to influenza which is stubbornly persisting in scattered areas in the US. What a crazy patchwork!

New Covid Isolation Guidelines

Maybe this has overshadowed everything in the news. I've discussed this recently in the blog and was expecting the new guidelines to come in April, but CDC bumped it up by a month. It incorporates new information about covid epidemiology, hospitalization rates, and outcomes with balancing for impacts on the economy and on school and work attendance into a comprehensive guideline for all respiratory infections. So, no longer do we have a specific number of days after covid diagnosis to remain out of school or work. The document has multiple links and is pretty complicated. The CDC's press release is a good summary, however. Note that vaccination is still stressed heavily, though I expect it will be ignored by the same hardcore group of antivaxxers. Here's the quick blurb:

"When people get sick with a respiratory virus, the updated guidance recommends that they stay home and away from others. For people with COVID-19 and influenza, treatment is available and can lessen symptoms and lower the risk of severe illness. The recommendations suggest returning to normal activities when, for at least 24 hours, symptoms are improving overall, and if a fever was present, it has been gone without use of a fever-reducing medication."

I am very much in favor of these new recommendations. Circumstances have changed, and we have learned a lot from management of the pandemic these past few years. I just hope our vaccination rate will improve and that people with any respiratory symptoms at all will be aware that they can pose a significant risk to others who may have circumstances putting them at high risk for hospitalization or death from respiratory viruses. Also, please note this only applies to community settings; there are no changes for healthcare settings.

Squirrel Redux

If I were superstitious, I wouldn't mention the fact that my neighborhood squirrels still have not attacked my newly-positioned bird feeder. I was bemused by an article in the Local Living section of the Washington Post last Thursday, clearly written by a squirrel lover. Squirrels do have value, and I have no desire to wipe them off the face of the earth. I just don't want them eating all my bird seed.

A friend of mine in South Carolina with an array of bird feeders and birds also has come to terms with squirrels, albeit somewhat differently than my crazy solution. He just monitors things, and when the squirrels reach a point that he feels they become a significant barrier to maintaining bird happiness and seed access, he uses a humane trap to collect squirrels and then release them far from his neighborhood. I won't disclose where he releases them, but it sounded like a good place for squirrels and unlikely to bother too many people. I wonder if any of them found their way back to him.

A downy woodpecker said hello to me last week.

Famous golfer Tiger Woods couldn't complete the second round of a golf tournament this weekend due to influenza. Two questions came to my mind immediately, still not answered. But, we have a lot more than golf to discuss this week.

WRIS

I suspect we are a matter of weeks away before I can retire Winter Respiratory Infection Season as a weekly feature. RSV is much less of a factor now, and I won't be discussing much about RSV unless things change.

Influenza-like illness continues to fluctuate regionally, we're really seeing wide variations. I'll mention again that this tracking method will pick up not just influenza, but also other respiratory illnesses. However, pre-pandemic it was a pretty reliable gauge of influenza activity. I do note that Mr. Woods lives in Florida and the golf tournament is in California. He became ill Thursday night, so using the common incubation period for flu of 2-3 days he could have acquired this in California (if he was practicing there a few days before); however, the outer range for flu incubation period is 7 days, so all bets are off about where he met his virus. (Also, I'm not stalking him, I have no idea about his travel history.)

At this stage of flu season, it's worth a look at pediatric mortality numbers. It's a little less than, but similar to, last year. Also note there is a significant lag time in reporting and verifying influenza deaths, so some of these bars in previous weeks will rise.

Pediatric deaths continue to occur slightly more commonly in children without underlying medical conditions, and the 5-11 year age group is the most common. Unfortunately, no data for vaccine status is provided.

What about the covid scene? As usual, I'm still looking at wastewater data because the methodology for collecting and reporting this information hasn't changed as much as have the methods for reporting infections and deaths among the states.

Again, this is at most a qualitative descriptor, but nothing to suggest a new surge approaching. Wastewater activity is highest in the South.

I wish CDC would publish numbers of covid pediatric deaths like they do for influenza. They only report death rates per 100,000 by age, and of course they are very low for the pediatric population. The absolute numbers are somewhere in there, but on the CDC website it would require me to write my own search language in their database, and I'm too lazy to spend the time to figure that out.

I also took a look at CDC's covid vaccine rates by age, especially since they now have updated information regarding the fall XBB vaccine dose. It's pretty grim.

Note that the highest rate is only 13.4%, and when I dug down into more details, all the states except one were in single digits for pediatric populations receiving the updated vaccine. The best and only double-digit rate was Vermont at a dismal 13.4%.

On the other hand, one could argue that because rates of serious pediatric disease with covid are so low it isn't cost-effective to vaccinate children who do not have risk factors. In fact, that's what most countries have decided; the US is an outlier in offering covid vaccine to healthy children. Nonetheless, on an individual basis every child is better off being vaccinated than not, even given the low risk of death, long covid, MIS-C, etc.

Back in the somewhat good news arena, a recent article gave an overview of planning (and funding!) for research on better covid vaccines, monoclonal antibodies, and antiviral drugs that will not be subject to loss of effectiveness with new variants. It's called Project NexGen.

Lastly on the covid front, many of you probably heard about CDC plans to change isolation guidelines for the public to be more in line with what we do for flu and other respiratory viruses. So far it is just a draft, but it's targeted for release in April. It's not really based on any new findings about transmission rates or duration of infectivity, but rather I think an attempt at simplicity with the recognition that current guidelines aren't being followed by the majority of the public anyway. What I think is most important, and I hope the final guidelines will stress, is that guidelines should differ depending on the situation. For example, it's a very different calculus for children attending school than it is for those same children going to visit their 85-year-old grandma. The public needs to understand that different risks occur in different circumstances.

Measles

Hot off the presses, 4 children in a single elementary school in Florida developed measles. So far not much official from the Broward County health department, but I'm betting that none of them were fully immunized. Watch out for a large number of secondary cases in the coming weeks.

Changes in Prophylaxis for Meningococcal Disease

This was news from the previous week that I'm just mentioning now. Ciprofloxacin has been used for prophylaxis of meningococcal disease for several years, but recently some sectors are now seeing resistance to quinolones. So, if you are considering prophylaxis of a close contact of someone with meningococcal disease, you will need to contact your local health department immediately to see if the resistance rate meets criteria for choosing an alternative agent such as rifampin, ceftriaxone, or azithromycin.

Tiger's Third Degree

I look at everything through an infectious diseases eye, whether I'm walking down the street, reading the paper, or chasing squirrels from the bird feeder; I just can't stop myself. So, I have 2 questions for Tiger.

  1. Did you get a flu vaccine this year? I'm not a betting man, and I've already made one bet in this blog, but I'd guess not. He had fever and other symptoms the night before his Friday golf round, and then Friday morning still had fever and other symptoms but tried to play the round, making it through a few holes before feeling faint and ending up with IV rehydration therapy according to his official statement.
  2. And to follow up on the above thought, what were you thinking trying to play the round on Friday? Not only did you not meet any school or workplace criteria for participating, you exposed everyone close to you to influenza presumably without notifying them. Of course, this is the sort of "tough it out" mentality that I've been guilty of myself in the past, at least to the point of working when I had a mild cold because I thought myself too essential for my workplace or didn't want to shoulder my colleagues with covering me. I don't think Tiger needed the money for playing in the tournament, but he also was the host of this particular event and I'm sure many fans turned out primarily because he was playing, so that's a bit more pressure than in my workplace. Still, isn't it time we made a change in our behavior when we're sick? Take a moment to think about the impact your actions have on others.

Which brings me to a third question for Mr. Woods: Would you at least make a statement recognizing that you should not have tried to play on Friday, and also give a plug for flu vaccine even if you didn't receive one this year?

I'd bet big bucks that Tiger Woods doesn't read this blog, so, yes, I'm just blowing off steam.

Next week is the regular meeting of the ACIP, I"m hoping to view most of the 2-day meeting and have this be the focus of next week's blog.

I've been a Super Bowl addict I think from Super Bowl I, persisting in spite of the fact that the NFL has done very little to limit head trauma and chronic traumatic encephalopathy. I'm usually tied to the Super Bowl screen almost continuously because I like to pay particular attention to the national anthem (more on that later) and to all the commercials. For Super Bowl LVIII I'll unfortunately need to grimace and grit my teeth when the Kansas City fans do their insensitive tomahawk chopping and war hooping.

As I rush to finish my long list of chores for today I somehow need to cull through this week's list of 16 blog topic ideas to post something with low soporific properties. Here goes.

I'm Beginning to Really Worry About Measles

It's difficult to find a central, accurate source of data, but it seems to me that an unprecedented level of sites around the world are experiencing high numbers of measles cases. Coupled with robust international travel, declining vaccine rates, and very high contagion, the US population could have a major resurgence.

An editorial in the BMJ last week (unfortunately freely available only to those with a subscription) re-sounded the alarm. The impetus was a new outbreak in the West Midlands, but really the problem has been sweeping Europe for at least a year. They quote other sources citing over 42,000 cases in European Union countries from January to November 2023, with 5 fatalities. Ireland, which had only a few measles cases in 2022 and 2023, reported the death of a middle-aged man who had visited Birmingham; no further details such as underlying risk factors are available presently. Our northern neighbors in Montreal report a measles case in an unimmunized child, likely acquired on a trip to Africa. The child's age isn't mentioned but he was apparently school-aged since a school is one of multiple sites where health authorities are trying to track down contacts.

I came across an updated measles website from the Infectious Diseases Society of America that I think is pretty helpful, including several links to other sites. Look at the Facts link for a good discussion of common measles misconceptions. And, please, please, please make sure all your eligible pediatric patients are immunized.

Speaking of Vaccine-Preventable Diseases

Diphtheria has killed 130 Somali children in the last 3 months, according to a news report. Antitoxin availability in the country is very limited. Diphtheria continues to pop up in resource-poor countries with ever-present risk of imported and then locally-acquired cases appearing in the US.

"Silent" ARF

A new study carried out in Sudan informed me about the existence of "silent" acute rheumatic fever. The investigators performed handheld echocardiography testing on 400 febrile children 3-18 years of age who did not have a definite etiology for their fever. Of 281 children who had no clinical features of ARF, 44 had evidence of rheumatic heart disease on echocardiogram. This is an interesting diagnostic intervention that could prove practical for use in high risk ARF countries, but costs and training could be significant barriers.

Thankfully we don't have much of a rheumatic fever problem in the US, likely because most endemic US group A streptococcal strains are unlikely to trigger ARF. However, imported strains certainly pose a risk, and evaluation of any suspected ARF case should take into account travel history/country of origin.

More on Treatment of Hearing Loss in Congenital CMV Infection

Last week I mentioned a small phase 2 study of late, short course treatment for children with hearing loss likely due to congenital CMV infection; it didn't work. Now this week we have a report of a small phase 3 study in the Netherlands. It was an unusual circumstance where a randomized trial was converted to a non-randomized trial because the original trial floundered due to lack of enrollment; most parents wanted their children to receive treatment. In the new study, children with hearing loss but otherwise clinically silent congenital CMV infection received either 6 weeks of oral valganciclovir (n=25) or no treatment (n=15). They were followed until 18-22 months of age, and the treatment group had less hearing deterioration than did the control group. Not the cleanest study but a better design overall than was the US study, and it did find evidence of benefit. This also points out the great difficulty in conducting these trials; even though congenital CMV infection is very common and virtually all US infants are screened for hearing loss, it's very difficult to enroll and follow-up these children in randomized double-blind placebo-controlled trials. We still don't have a definitive answer on treatment benefits for isolated hearing loss in congenital CMV, but I hope the investigators don't give up trying.

Alaskapox

No, I didn't make up that word, it's a real orthopoxvirus that can rarely infect humans mostly in, you guessed it, Alaska. Only 7 human cases are known to exist, but the most recent one, in an immunocompromised man, was fatal. The report also is striking for how long it took to diagnose him. The virus mainly infects small mammals (voles, shrews) with no known human-to-human transmission so far. However, there is no reason it wouldn't be spread from another human, just like other viruses (smallpox, cowpox, Mpox) in the same family.

Photo from https://health.alaska.gov/dph/Epi/id/SiteAssets/Pages/Alaskapox/Alaskapox-FAQ.pdf.

New Syphilis Testing Guidance

CDC released new recommendations for laboratory testing for syphilis, good timing given our terrible syphilis epidemic in the US. It is highly technical, so mostly of interest to laboratorians and syphilis geeks like me. Some of the illustrations and graphs are useful for everyone. Here is a nice quick view of lab test results in various syphilis stages:

And an explanation of the prozone effect, very important and something that I've found not all hospital clinical lab personnel understand. It appears mostly with RPR testing, where very high antibody levels cause a false negative result unless the assay is run at higher dilutions.

WRIS

Not a whole lot new with the Winter Respiratory Infection Season.

Investigators in France reported that rhinovirus infection in infants was a major contributor to bronchiolitis hospitalizations pre- and during the pandemic. Here's an example of ventilator use for RSV and rhinovirus during 2019 - 2020.

From a practical standpoint we have a tough time sorting this out with commercially-available testing. PCR testing for rhinovirus uses primers that include most enteroviruses, so you will always see these results combined as rhinovirus/enterovirus with no way to separate out which is which. The problem is compounded because most enteroviruses normally persist in the body and in nasal secretions weeks to months after the clinical illness resolves. So, a positive rhino/enterovirus test might reflect an infection that a) occurred months previously, and b) could have been asymptomatic (90+% of enteroviral infections are asymptomatic). Often we can guess rhinoviruses are active if we see a mid-winter bump in rhino/entero positivity, since the usual enterovirus epidemic peak is late summer/early fall.

Of note, the French investigators did not provide details of the PCR assay used in their study, so we are left trusting the journal editors that it did reliably distinguish rhinoviruses from enteroviruses.

RSV is pretty clearly on the way out, though still causing a lot of illness nationwide. The decline is present in all 7 monitoring sites.

Influenza also is declining, with a couple caveats.

First, we are starting to see a higher percentage of influenza B isolates now. This typically happens near the end of flu season, but it could also produce a secondary bump in infections. Second, local and regional flu levels are quite variable - what's true for Maryland is completely different in New Mexico. Also, I've never been a fan of presenting city-level (NYC, DC) data in the same context as state data - a classic apples and oranges comparison.

Covid wastewater data continue to be encouraging.

We also have a few new updates on the covid scene. The UK released their spring vaccine recommendations which are to offer vaccine (usually mRNA XBB.1.5 vaccine unless not suitable for an individual) to adults 75 years of age and older, residents in adult care homes for older people, and anyone 6 months of age or older fulfilling their definition of immunosuppression.

I was pleased to see an update on trying to get a handle on Postacute Sequelae of SARS-CoV-2 in Children (PASC), though as I read through it I still felt it was a difficult jumble of clinical syndromes that make it hard to develop practical management advice anytime soon. Here's an overview of their conceptual model:

I applaud the investigators for continuing to slog through this and I do expect to see concrete advice sometime in the future, not only for PASC but perhaps for all those other post-infections syndromes currently lumped into the myalgic encephalomyelitis/chronic fatigue syndrome wastebasket.

Birdhouse Update

I'm sure everyone has been waiting to hear the latest update in my birdhouse squirrel-proofing adventures. I'm happy to say the birds are back, but so far no squirrels are stealing the birdseed! I did notice one dastardly Scurius representative sitting on the large branch from which the birdhouse was suspended, but it never made an attempt to jump. We'll see how long this holds up.

White-breasted nuthatch enjoying the sun and safflower seeds, unmolested by squirrels.

Super Bowl VIII

Yes, I'm aware it's now LVIII, but much of my Super Bowl roots go back to the one 50 years ago where I happened to be employed selling beer in the stands. I didn't make much money; I was assigned to the Vikings side of the stadium, and they got blown out by the Dolphins and quit buying. I also didn't see much of the game itself due to walking up and down the stands, yelling "cold beer" and looking for raised hands.

I was required to show up several hours before kickoff time, and the stadium was virtually empty. One person on the field that morning happened to be one of my personal heroes, the country singer Charley Pride. (As an ironic note to me, he died of covid complications at age 86, in the first year of the pandemic and before vaccine availability.)

Pride was really the only Black person to have broken through as a country music star at the time, and he was practicing singing the national anthem which he would do at the start of the game. When he finished practicing I walked down to the field level and he was kind enough to chat with me a few minutes. He autographed my flimsy paper vender tag, now lost somewhere during my many moves.

As you can tell, I haven't lost that 50-year-old wonderful memory. Kiss an angel good mornin' if you have a chance. 😉