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Month: November 2024

Published on Leave a comment on The Wiedermann Thanksgiving Massacree of 199?

Thanksgiving week has arrived, which for me means making checklists and time schedules and then revising them several times up until Thursday, at which point nothing happens according to schedule and I just go with the flow. It's also a time I remember the infamous Wiedermann Thanksgiving Massacree of 199? (I can't remember the exact year), with apologies to Arlo Guthrie.

Understandably in the past few years, this blog has drifted to the latest public health and epidemiologic trends, but I'm comforted by the fact that respiratory infections remain relatively calm and that this past week's publications allow me to focus more on recent original studies of interest to pediatric healthcare providers and the general public.

Macrolide-resistant Mycoplasma pneumoniae

I'm getting pretty tired of hearing about our resurgence of "walking pneumonia," but this article caught my eye. It's a report from North Dakota, and my interest wasn't in the fact that the investigators found evidence of macrolide resistance; that's nothing new. The bigger question is whether the resistance has major clinical significance. I've stated previously that, because Mycoplasma lower respiratory infection is largely a self-limited disease, it's difficult to know whether antibiotic treatment helps, and if it does, whether the amount of benefit is worth treating with antibiotics. The vast majority of "walking pneumonia" cases in children don't need any nasal swab or radiographic testing, nor any treatment.

The study was small, just based on 10 children of which 8 had macrolide resistance genes detected in their nasal swab assays. Six of them were said to have failed azithromycin treatment, though the authors didn't define treatment failure. Six of the patients who had fever and received doxycycline or levofloxacin became afebrile within 24-48 hours. Needless to say, this doesn't translate to great evidence that macrolide resistance is clinically important; it does point to the fact that we need randomized controlled trials to answer this question. Unfortunately, studies need funding, and this condition isn't likely to be profitable enough for funding from a pharmaceutical company. My only takeaway from the study is that further evaluation and treatment should be considered in children with possible pneumonia in whom symptoms worsen or fever persists more than a few days. Unfortunately, M. pneumoniae susceptibility testing isn't routinely available. For mild community-acquired pneumonia in children, amoxicillin is the treatment of choice, with azithromycin as a second-line agent. Switching to doxycycline or levofloxacin should be reserved for macrolide treatment failure, however that is defined.

Certainly we are having a banner year for mycooplasma respiratory infections, likely a combination of the normal mycoplasma surges we see every few years and lack of exposure during pandemic years. Which brings us to ...

Immune Debt

I really liked this new article that looked at the concept of a dose response effect in immune debt, i.e. that the magnitude of illness we see in rebounds of respiratory infections post-pandemic should be proportional to how much less frequent these infections were during the pandemic. The statistical methods in the study are somewhat beyond my expertise, but I mostly think the authors proved their point that lifting of non-pharmaceutical interventions (NPI) around the world seemed to be a point of increase for various respiratory infections. Here's a sample of the findings.

If this is all true, presumably we'll be back to the "old normal" of seasonal respiratory infections soon (barring another serious pandemic).

UTI Diagnosis

I must confesse my eyes rolled when I saw the title of this new study. Early in my career I was involved in UTI research. I've been very disappointed in analyses of UTI diagnosis in recent years because most of them seemed to ignore how variable accuracy of different UTI diagnostic laboratory methods are, even for something as basic as urinalysis. For example, it makes a big difference whether the number of white blood cells in urine is determined by machine (usually flow cytometry), manual counting by a lab technician with or without use of a hemocytometer, or just a urine leukocyte esterase dipstick. So, I was very pleasantly surprised that this group of investigators highlighted precisely those concerns. This was a study of around 4000 febrile children evaluated for UTI with urinalysis and culture, and the results showed that virtually all urinalysis components were poor at predicting a positive urine culture, defined as > 50,000 cfu/mL of a single pathogen in a catheterized urine specimen. The authors concluded that around 20% of children with febrile UTI could have normal urinalyses but also acknowledged how difficult it is to factor in asymptomatic bacteriuria (estimated rate 2%, but tough to assign an exact number) and specimen contamination. I don't think this study solves any of these issues, but it is an important contribution to our understanding of UTI diagnosis.

WRIS and Nowcasting

Last week CDC published a more detailed explanation of how the time-varying estimated reproductive number (Rt) can be used as an early warning for changes in respiratory pathogen transmission activity. This report is of interest mostly to true epidemiologic nerds, so of course I found it very enlightening. The authors did provide convincing evidence that this methodology has been working well recently.

We're not due for another respiratory illness outlook update from the CDC until mid-December, they only provide these every 2 months, but we remain mostly quiet. I suspect we'll see RSV and influenza hit pretty soon around the country. Again, you can check your own local illness and wastewater activity at the CDC' site.

Beware Studies Based on Administrative Data

This is one of my pet peeves: not the studies themselves, but how too much importance seems to be given to them in the lay press (bolstered by academic organizations seeking to get their names in the news). A new study shows how variable results can be from these databases, using the example of invasive bacterial infections in febrile infants. It's easy to imagine how any system based on diagnosis codes entered into various databases could lead to classification errors, but this report provides an excellent example to keep in mind. Any study using an administrative database should evaluate accuracy of diagnoses on a subset of patients to give some evaluation of the accuracy of their results (IMHO).

New 2025 Vaccination Schedules Published

The information isn't new, just based on prior FDA and ACIP deliberations mostly happening over the summer, but now we have the colorful schedules to use. The AAP has a quick summary of changes.

Happy Thanksgiving!

I have so much to be thankful for this year, and I hope not to repeat the Wiedermann Thanksgiving Massacree of maybe 30 years ago. I won't explain in full; it's too painful to spend anything like the 18 minutes, 34 seconds that Arlo Guthrie took to explain his Alice's Restaurant Thanksgiving Massacree of 1965. (Restaurant namesake Alice Brock died a few days ago.) The short version is that my attempt to create the perfect turkey gravy ended badly in an oil slick of glass shards in the kitchen. Why I'm still allowed to have any Thanksgiving responsibilities at all is a prime example of my wife's incredible powers of forgiveness.

We'll be hosting a relatively small gathering at our place this year. My duties are limited to turkey, gravy, and drinks. Starting today I'll have my checklists made out, separated into daily tasks. Thursday itself will have a well-choreographed timeline to include oven and stove use times in our smallish kitchen. As I said at the start, these scraps of paper will bear little resemblance to how the meal actually unfolds.

I won't go into detail about all the food-borne illnesses linked to turkey dinners, but please make good use of your food thermometer and follow guidelines.

And, speaking of Arlo, some of you might be interested in his live recording of "Amazing Grace" with Pete Seeger in 1993 (around the time of the Wiedermann Massacree!). It's 13 minutes of music and meanderings still meaningful in today's world.

Published on Leave a comment on All Politics is Local

U.S. Representative Tip O'Neill popularized this phrase in the early 1980s, but perhaps it lost its meaning in later years. Has that changed? Infectious diseases, on the other hand, are most certainly not local.

Infectious Diseases Abroad

Any ripple in communicable infectious diseases in one locale inevitably affects others in far-away locations. Last week saw a number of ripples.

(Not) Measles in American Samoa

Yes, I'm aware that American is a US territory, but it certainly qualifies as far-away.

In 2023, health authorities in American Samoa went on a wild goose chase based on non-recommended testing practices of a suspected case, resulting in a large expenditure of time and money with no benefit. I'm not faulting Samoan practitioners, they had to deal with a lack of available testing resources in the setting of an island rocked by a deadly measles outbreak a few years ago; that outbreak had been fueled in part by prominent anti-vaccination proponents. This recent episode should serve to remind us of proper use of measles diagnostic testing which relies most prominently on use only for individuals who fulfill proper case definitions.

The above report was in last week's MMWR which also contained a WHO measles update. Here's a comparison of 2000 and 2023 measles cases and deaths (note North America is not included in these numbers.)

Severe Avian Influenza in Canada?

Last week Canadian officials confirmed that a critically ill teenager is infected with influenza A H5N1. The source is still unknown, and no close contacts are known to be infected. It's been very tough to get details about the patient's illness, but after going through a transcript of a British Columbia health official's briefing on November 12, it seems that the previously healthy child presented with typical H5N1 symptoms of conjunctivitis, cough, and fever, but then several days later had deterioration. That sequence of events, a sort of biphasic illness, is classic for secondary bacterial complications of influenza. Influenza virus infection of any type can be complicated by secondary bacterial processes, including sepsis and toxic shock syndrome, usually several days after initial flu symptoms begin. Canadian authorities haven't provided any more details, but I wouldn't be surprised if this is what's going on. I'm hoping it was recognized quickly and his healthcare team can return this person to normal health.

Along these lines, NASEM just issued a new publication detailing research priorities for avian influenza A H5N1 readiness. Some of this is already happening, and I hope funding priorities will continue to support planning.

Mpox Update

Last week WHO updated the status of the mpox outbreaks across Africa, a mixture of good news and bad news. Priorities are delivering vaccine to those at risk and implementing newer PCR testing for mpox just approved by the AfricaCDC. Also this past week we learned of the first mpox clade 1 case in the US, occurring in a traveler returning from Africa.

Number Needed to Vaccinate for Covid in the UK

I've mentioned in previous posts that the UK recommends many fewer groups for covid vaccination than we do in the US, primarily because of cost considerations. Last week the UK's Joint Commission on Vaccination and Immunization gave us a bit of a closer look at how those decisions are made with some NNV calculations. NNV (along with its cousin Number Needed to Treat for medication) are a good way to explain "bang for the buck." NNV simply refers to the number of individuals needed to vaccinate to prevent one additional case of the infection, compared to no vaccination. It depends on many variables including the rate of the disease and the number of susceptible individuals in the community and the vaccine effectiveness. Also, NNVs vary with the outcome of interest, such as infection versus hospitalization versus death. It's increasingly harder to calculate NNVs for covid vaccine because of asymptomatic infections and less widespread testing being performed.

The JCVI didn't give us NNVs for all age groups, but they did provide a close look at pregnant people and infants under 3 months of age, the latter group of course not eligible for vaccination and dependent on maternal immunity passed to them transplacentally. I had to dig into attachments to the reports, but here's the bottom line: NNV to prevent hospitalization of a pregnant person is "just under 2000" and "around 300,000" to prevent severe hospitalization. I couldn't find a definition of severe hospitalization but from the context it appears to be something more than overnight observation but less than ICU admission.

For infants < 3 months of age, NNVs (for maternal vaccination) were "under 500" for any hospitalization, "just over 13,000" for severe hospitalization, "almost 190,000" for ICU admission, and ranged from 380,000 to 1.5 million for mortality, the latter extremely hard to calculate due to rarity of the outcome. (But we're all thankful that it is rare.)

Just for comparison, NNV for flu vaccine to prevent 1 additional outpatient visit or 1additional hospitalization in children 6 - 59 months of age ranged from 12 - 42 and about 1000 - 7000, respectively, in one study.

Novavax Combination Covid-Flu Vaccine Study Allowed to Resume

I mention this item mostly to show how well our vaccine safety oversight is working. This study was paused when 1 phase 2 study participant developed what was initially diagnosed as motor neuropathy (with concern for Guillain-Barre syndrome) but then turned out to be amyotrophic lateral sclerosis, not an inflammatory disorder plausibly related to vaccination. This is one of many mechanisms for detecting evaluating rare events after vaccination. Novavax now can proceed with phase 3 studies.

E. coli O157:H7 Outbreak Numbers Grow ...

... but not related to ongoing infection, simply reflecting a delay in case reporting/verification. CDC and FDA report we are now up to 104 cases spread over 14 states. Of the 98 persons with more detailed information available, 34 were hospitalized and 4 developed hemolytic-uremic syndrome. "Of the 81 people interviewed, 80 (99%) report eating at McDonald's. Seventy-five people were able to remember specific menu items they ate at McDonald's. 63 of 75 people (84%) reported a menu item containing fresh slivered onions."

The case map strongly resembles the distribution map for the suspected onions which are now out of the food chain.

In the meantime, we have another E. coli O157:H7 outbreak, this time associated with carrots. [Correction added 11/18/24: this outbreak is due to E. coli O121, not O157:H7 as originally stated.]

I have a feeling I'm going to be washing my salad items more carefully for a while!

WRIS

The winter season still hasn't started, so I'm reduced to browsing the wastewater maps, all updated through November 14 and current through November 9. Here is maybe a look at things to come. First, here's covid:

Now flu (wastewater only tracks influenza A):

Last but not least, RSV:

I'm a Throwback

When I started practicing medicine, implicit in my professional obligations was the duty to do my best to treat anyone who presented to me, without regard to their backgrounds including race, gender, sex, legal status, and, I guess must be said in today's world, political affiliation. Having practiced in Washington, DC for over 40 years, that last category came up frequently as I encountered parents who were elected officials and/or involved in jobs in the political realm. In keeping with that sentiment, I'll still be keeping politics out of this blog and restrict my pontification to infectious diseases. I'll also avoid commenting on various conspiracy theories and other wild ideas emanating from individuals with no scientific basis for their claims. I will, however, comment on any proposed policies related to pediatric infectious diseases where scientific analysis can enlighten the discussion. Nuff said for now.

Published on Leave a comment on A Modest Proposal

Quite an eventful week! In general, I try to keep politics out of my commentary, though I fell short of this goal in my February 25, 2024, post where I blasted the Surgeon General of Florida; that may be the only time I've singled out an individual in a negative manner in this blog. Now, I find that his name is being mentioned as the next Secretary of Health and Human Services. All of this reminded me of an almost 300-year-old pamphlet.

But first a bit of the other health news from last week.

Mayaro Virus

In spite of my voracious appetite for medical knowledge, the list of viruses I've never heard of is lengthy. Now my list is one item shorter due to a new report. Mayaro virus is another of the arthropod-transmitted alphaviruses prevalent in parts of South America, causing a febrile illness with severe arthralgias very similar to its cousin Chikungunya virus. Primates serve as a reservoir with the primary vector the mosquito Haemagogus janthinomys. If like me you are a bit shaky on some elements of South American geography and history, Suriname is a former Dutch colony located just north of Brazil and has territorial disputes (in light green) with neighboring countries.

Measles in Vietnam

Vietnam is introducing earlier measles vaccines to try to stem an epidemic. In this WHO Western Pacific region report, you can see Vietnam is going the wrong way in measles incidence. Like the rest of the world, we all "enjoyed" a pandemic period where many traditional infectious diseases transmitted by respiratory routes showed significant declines due to non-pharmaceutical interventions, only to now reappear in greater numbers. For measles, Vietnam showed an incidence of 7.4/million population in 2020, dropping to 0.3 in 2022 but now back up to 7.1/million in 2024.

Normally Vietnam recommends measles immunization at 9 months of age, but now this is being dropped to 6 months due to an increase in cases in younger age groups. (You'll need Google translate for this link.)

Computerized Radiograph Interpretation for TB?

Although this study was performed only in adults, I thought it was worth mentioning as a possible glimpse of the future. Investigators in Africa and southeast Asia looked at the performance of a computer program to interpret chest radiographs in about 1400 adults with cough > 2 weeks in duration and found the program to have significantly higher sensitivity than a relatively new blood test for host response gene activation in TB as well as superior to CRP. When trying to diagnose TB in resource-poor settings that may not have access to good molecular and other microbiologic methods for TB diagnosis, we need every tool available. I'll be interested to see how newer methods for TB diagnosis evolve.

More on Bird Flu

CDC reported that 7% of 115 dairy workers at farms known to have infected cows showed serologic evidence of influenza A H5N1 infection. Four of the 8 seropositive workers did not recall having any respiratory signs or symptoms since the cows were first noted to be sick. This rate wasn't terribly different from the 60% of those with no illness history in the seronegative group. Given that H5N1 so far seems to be a mild illness in humans, the finding of asymptomatic infection isn't surprising. Clearly we need a lot more data on human illness in these and other settings.

Benefits of Quadrivalent Meningococcal Vaccine

Of our recommended vaccines, meningococcal vaccine probably has the lowest "return on investment." Meningococcal disease is relatively rare but comes with very high morbidity and mortality when it does occur. This modeling study estimated the number of cases of invasive meningococcal disease in 11-23 year-olds prevented by vaccination during the period 2005-2021. One always needs to take modeling studies with a grain of salt because they by necessity make a lot of assumptions. The authors did a good job of trying to look at all possibilities. They concluded that "vaccination averted an estimated 16 (95% CrI, 8-31) deaths among adolescents aged 11 to 15 years and 38 (95% CrI, 19-75) deaths among those aged 16 to 23 years." I guess those are small numbers when compared to the entire US population, but this is still a meaningful benefit.

WRIS

Things are still relatively quiet, though with regional variations.

I did happen to note that wastewater levels of RSV are very high in Maryland, so maybe that will be the first pathogen to increase in my region.

Make America Healthy Again

I feel like the MAHA acronym was one of the nicer-sounding political slogans to appear recently. However, the fact that it was popularized by a notorious pseudo-science fringer concerns me for what might lie behind MAHA. That made me recall a short treatise by Jonathan Swift (of Gulliver's Travels fame) that I came across a long time ago. I read it again a few times this week, and this highly satirical essay entitled "A Modest Proposal" is worth 10 or 15 minutes of your time. I think it is best read without knowing where the narrator is going, so I'll give you a SPOILER ALERT. You can read the original document in the link now, before reading what I write below, or you can just forego the surprise and keep on with my take below.

The narrator beings with an "objective" view of the problem, in 18th century Ireland, of the economic woes of a large section of the populace. He particularly hones in on the difficulties that parents in lower economic strata have in providing for their children. After going through some numbers assumptions that we can only guess at the accuracy, he decides that Ireland has about 120,000 children born to impoverished parents annually. How can the country solve this problem? He offers his modest proposal, or "humble solution:" It's a sudden turn in tone, to say the least.

"I have been assured by a very knowing American of my acquaintance in London, that a young healthy child well nursed, is, at a year old, a most delicious nourishing and wholesome food, whether stewed, roasted, baked, or boiled; and I make no doubt that it will equally serve in a fricasee, or a ragoust."

Yes, Mr. Swift in his satirical essay is proposing cannibalism as a solution to poor families trying to raise their children. He goes on to describe various details of preparation and serving.

MAHA sounds OK now, but I fear of this becoming another modest proposal. I'll withhold my judgment until we see more details of the plan.

Published on Leave a comment on Fall Back

Once again I find myself, an ostensibly tech-savvy individual,* faced with manually resetting the time on 11 clocks and appliances in my house. Only my phone, laptops, and tablet appear to have joined the 21st century by self-correcting to eastern standard time. Of course, if our country had truly joined the 21st century, we wouldn't be making this twice yearly switch in the first place.

My election anxiety is somewhat mollified by focusing on infectious diseases, so you can categorize the following as therapeutic in nature.

WRIS

Still not much going on, though I was intrigued that my state of residence is 1 of only 2 to show up with moderate respiratory illness activity last week.

I'm pretty impressed by how quiet the SARS-CoV-2 front is. However, it's still around, and we can expect to see a resurgence sometime.

The fact that influenza has not yet appeared might indicate we are returning to a more "normal" flu season. The graph below shows how different the prior 3 flu seasons were from pre-pandemic experiences, where last year had a very early peak and 2020-21 and 2021-22 had very low and atypical peaks. (Apologies for CDC's labelling here, but if you stare at it long enough you can pick out which line goes with which year.)

New Development in Bird Flu

The so-called highly pathogenic avian flu H5N1 cropping up in dairy and poultry farms and in wild bird populations has been in the news for many months now. It still seems to be a mild illness in humans, most of whom have direct exposure to these farms. Only 41 humans have confirmed infections in 2024 so far. What's a bit noteworthy this week is that the virus may now have shown up in pigs. USDA officials reported probable swine cases at a backyard farm in Oregon where poultry, cows, and pigs all mingle. The farm itself has no role in commercial production of any foods, so it isn't a risk to others. What is of slight concern is the fact that pigs are involved. Pigs have a special place in influenza science because they have both human and avian flu receptors in their respiratory tracts, making the chance for a recombination event to occur if they happen to be infected with human and avian viruses at the same time. Most of the time this doesn't cause creation of a new pandemic strain, and I wouldn't hit the panic button at all now. Actually I'm surprised it took this long for swine infection to be found. The affected animals were all euthanized and multiple studies are ongoing, so I'm sure we'll hear more about this.

Polio

The news isn't great as both wild and vaccine-variant polio cases continue to be reported. This Global Polio Eradication Initiative map is a good summary.

No new cases have been reported in Gaza, with just the 1 case confirmed so far. The interrupted vaccination campaign in northern Gaza restarted this week.

Dengue Still Going Strong

I was browsing the CDC dengue page this week; infections are still plentiful.

Puerto Rico has the greatest number by far, but note that we have had autochthonous (locally acquired without travel to endemic areas) dengue in the mainland US (California with 11 cases, Florida with 49).

*

Can I really claim to be tech-savvy? I think so. I have an advanced degree in educational technology with classes that included instruction in networks and the various hardware involved; the fact that my schooling ended in 2008 shouldn't disqualify me. Also, this past week I restored to full health our K-cup brewing machine that became confused and wouldn't deliver the appropriate coffee volumes or allow the correct menu choices in its buttons. I guess in the interest of full disclosure, when I couldn't find a satisfactory replacement brewer online, my astute intervention was reading the instruction manual, realizing that I hadn't ever de-scaled the device in the approximately 90 years I've owned it, and made it new again using only a low-tech tool (vinegar).

In spite of my skills with technology and vinegar, I'll be performing my semiannual time resets for the foreseeable future; I could never part with my grandfather's clock.

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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