Earlier this morning, Punxsutawney Phil saw his shadow, guaranteeing 6 more weeks of winter darkness with about the same amount of scientific basis as what we might be facing with a darkened CDC and other federal agencies. The original executive order limiting information release from federal agencies was said to last until February 1, but a day later MMWR is still silent.
We have now missed 2 MMWR reports, and I haven't been able to find any update on when/if this valuable resource might reappear. FluView Interactive and other CDC sites have similar notices though apparently are publishing some updates, which I'll show in the WRIS section later. Meanwhile, the world goes on.
Niger Eliminates Onchocerciasis Transmission
WHO announced that Niger joined Colombia (2013), Ecuador (2014), Guatemala (2016) and Mexico (2015) in eliminating transmission of Onchocerca volvulus, the cause of "river blindness." This is a major achievement, and I hope that funding cuts don't hinder WHO's disease elimination programs significantly.
African Outbreaks with Worldwide Significance
Sudan Virus in Uganda
This virus is in the Ebola virus family, and now Uganda is facing a new outbreak mostly involving healthcare providers (so far). WHO is advising against instituting any travel advisories, but the US State Department has had a Level 3 travel advisory in place since October, 2024, unrelated to any infectious disease outbreaks. (I was interested to note that this State Department site had no disclaimers about revamping the web site.)
Many readers will remember how Ebola virus came to the US via international travel. Certainly this new outbreak is still low risk for international spread, but the possibility remains and reminds all of us how distant outbreaks can hit home.
mpox
A new report in NEJM nicely describes the ongoing mpox outbreak in the Democratic Republic of Congo and surrounding areas. As emphasized in the accompanying editorial, spread from household close contact is prominent, with children sometimes experiencing severe disease. Pediatric cases are further described in another report, and the accompanying editorial emphasizes the challenges in trying to manage the outbreak. If you really want to dig deep into the numbers, WHO has an update. International spread so far has been limited but could increase.
MIS-C Phenotypes
This article caught my eye, even though MIS-C is less of a concern in our current covid situation.
The figure below is complicated, but suffice to say the researchers identified 3 clinical clusters: respiratory (cluster 1 above), shock/cardiac (cluster 2), and mild disease (cluster 3).
WRIS
Winter respiratory infection season is in full swing. It's not exactly great timing to have confusion in CDC's information restrictions during what is likely the height of flu season, not to mention ongoing concerns about avian flu. Already we were dealing with less data after the pandemic ended, a reasonable plan given less urgency surrounding covid. However, I admit to being confused about what might be changing in other surveillance systems now, with nary a peep (pun intended) about how the new administration's executive orders affect disease surveillance.
For what it's worth, here's a little bit of what I can find. I'm guessing that nothing much had changed with data collection methods by January 25, the closing date for the numbers used below.
Paul Simon has criticized most of the early work of Simon and Garfunkel, but the song that begins with "Hello darkness, my old friend" apparently is an exception. He is quoted in a 2023 interview regarding The Sound of Silence, “Somehow that song has changed its meaning over the years. It’s different. That’s good luck for me that that happened, you know?” I agree.
People talking without speaking People hearing without listening
I didn't have any trouble thinking of things to be thankful for this Thanksgiving-time. That might seem odd given the horrific events on the world stage now, and I don't mean to minimize that, but gratitude can coexist with dismay.
First, let's get caught up on this week's ID happenings.
Disappointing Measles News
Measles is probably the most easily transmissible human infection known; a high level (probably 95%) of population immunity is needed to prevent outbreaks. Not surprisingly, a breakdown in immunization rates during the COVID-19 pandemic likely is to blame for increases in measles cases worldwide, as reported last week by the CDC. Concomitant with a decrease in measles-containing vaccine coverage from 86 to 81%, measles cases increased 18% (7.8 million to 9.2 million) worldwide from 2021 to 2022; deaths increased from 96,000 to 136,200. Still, and here's the thankful part, vaccination likely prevented 57 million measles deaths from 2000 to 2022. Here's hoping we can get our global immunization campaigns back on track.
2024 CDC Recommended Immunization Schedules Are Available
Even earlier than advertised, CDC has posted the 2024 immunization schedules. Primary care providers should study these closely due to some complex changes, particularly for pneumococcal and meningococcal vaccines. The AAP has posted a summary of key changes (click on the PDF link). As an aside, I'm a bit irked by what CDC and others call "shared clinical decision-making." Here's CDC's tool for SCDM for meningococcal group B vaccine:
I'm not a primary care provider, but I don't see a lot of help for busy frontline practitioners here. What we really need are more details about choices parents and patients need to consider. Specifically, what are the risks of not getting the vaccine versus those being vaccinated? As stated in the table, meningococcal B infections are relatively rare in the US, so vaccination isn't going to prevent much disease or mortality even with a highly fatal infection. The risks are different depending on individual circumstances. Are frontline providers supposed to have these numbers at their fingertips? Maybe the CDC or AAP will provide them. (Or, if not, maybe I will!)
MIS-C Cardiac Follow-Up
Multisystem inflammatory syndrome in children (MIS-C) following covid infection is very uncommon currently, but we shouldn't forget about monitoring children as they recover from MIS-C. A group at Children's Hospital of Los Angeles reported that even children who did not have clinical cardiac involvement during their acute illness still had some evidence of cardiac injury at the 6-month followup period. Most of the report deals with laboratory, imaging, and other testing, but of the 69 patients evaluated at 8 weeks 15 had clinical symptoms such as chest pain, palpitations, exertional dyspnea, or fatigue. The rate of clinical symptoms was actually lower in the group with no initial myocardial injury, although the difference was not statistically significant. The bottom line: make sure all MIS-C patients have good cardiology followup.
Variations in Influenza Antiviral Use
A group from Vanderbilt reported wide variation in prescribing practice for influenza antivirals during the period 2010-2019 (so, not affected by the pandemic). It is an administrative database study, a study design type that has inherent inaccuracies due to how administrative data is collected. In general, however, a wide variation in practice is an indication that something isn't right. Guideline-concordant compliance was low, for example <40% in children less than 2 years of age, a high risk group. I would have liked to have seen how flu vaccine status affected antiviral use since vaccination greatly lowers risk for severe adverse outcomes, but apparently the database did not contain that information. This is another opportunity for shared clinical decision making with parents; what are the specific rates for infection, hospitalization, etc versus medication side effects (primarily vomiting with oseltamivir) for an individual child, based on their risk factors? That's what a frontline health provider needs when discussing whether to treat a child for influenza.
The "New Normal"
I mention this catchphrase only to bury it. Not only does it seem nonsensical to me, it also is beyond retirement age. Some might wish to apply this catchphrase to the upcoming winter season. I'm strangely thankful/hopeful for this because it now appears we may get to see what a typical respiratory virus season looks like in the post-pandemic era. We haven't seen any weird covid upticks early on, and RSV looks more typical so far without the very severe season we saw last year. Flu may be starting to increase, similar to pre-pandemic seasons. Of course, all of the respiratory virus seasons vary somewhat from year to year. Will covid settle into just another winter respiratory virus?
FLUVIEW is back in business, and the map is heating up especially in the South.
Remember that this is a map of "influenza-like illness" so can capture other respiratory viruses. However, covid wastewater tracking hasn't had much of an uptick.
RSV-NET continues to show increase primarily in younger children, not matching last year's peak but possibly similar to prepandemic waves.
Happy Thanksgiving
I was looking around for something uplifting and fun to mention and happened on "Thanksgiving" by Edgar Albert Guest. Here's an excerpt:
"Greetings fly fast as we crowd through the door
And under the old roof we gather once more
Just as we did when the youngsters were small;
Mother’s a little bit grayer, that’s all.
Father’s a little bit older, but still
Ready to romp an’ to laugh with a will.
Here we are back at the table again
Tellin’ our stories as women an’ men."
I had never read anything by Guest, but I was sold on him when I read his Wikipedia page. Anyone who merits mention by Edith Bunker from "All in the Family," Lemony Snicket, Mad Magazine, and Benny Hill is my kind of guy. Furthermore, Dorothy Parker of Algonquin Round Table fame had the best line: "I'd rather flunk my Wassermann test than read a poem by Edgar Guest." I think maybe she wasn't a fan, but at least she knows her 1950s syphilis testing.
Last week I was a bit obsessed with all the leaves around my house, both on the ground and still in the trees. With a neighborhood leaf collection looming and many leaves still to fall, I decided not to rake that day. The next day I reversed my stance, which was a bad idea.
On the COVID Front
Although we aren't seeing much of a surge so far (see Tripledemic below), I did come across a few items to mention.
First, FDA issued an alert about potential dosage errors with the Moderna vaccine for children 6 months through 11 years of age. The standard dosage is 0.25 ml, but apparently the single dose vials contain "notably more" than this amount. So, if one draws up the entire contents of the single dose vial and administers it, the dose will be too high. Try as I might, I was unable to determine how much above 0.25 ml "notably more" is. So far the overdosage hasn't been shown to cause any harm. Please alert your staff to this.
On the topic of Multisystem Inflammatory Syndrome in Children, a prospective cohort study in the Netherlands suggests that MIS-C is lessening recently, possibly related to prior immunity. This fits with other reports, mostly anecdotal.
Finally, and consider this a very preliminary observation, researchers in China have noted an apparent increase in situs inversus diagnosed with prenatal ultrasound following lifting of covid restrictions in that country.
I'm advising caution in interpreting this study because 1) it is a short letter to the editor so methodologic details are a little sparse (supplementary online appendix helps); 2) funny things can happen when an epidemiologic blip is noticed that then triggers a look back - although the authors claim their protocols for performing sonography didn't change, all sorts of bias can affect the data in this setting; and 3) no one else has reported this association previously. I'm sure we'll see further refinement on this topic from these and other investigators in the coming months.
Some readers may have noticed I haven't mentioned anything about SARS-CoV2 variants for a while. They are still out there, changing rapidly as usual, but I won't comment much until/unless we see emergence of a variant dramatically different in its ability to alter epidemiology of disease, either by evasion of prior vaccine and infection immunity or with increased virulence.
New Infant Hepatitis C Screening Recommendations
CDC has issued new screening guidelines for infants born to mothers with hepatitis C, which should help identify infants at risk earlier. The entire document is very well written and informative. Expect updates to appear in the Red Book and from other organizations. Here is the bottom line for primary care providers, including a definition of perinatal exposure.
For a child not screened in early childhood:
Hepatitis C testing is a bit confusing to many providers; don't hesitate to seek assistance from your friendly neighborhood pediatric ID or GI provider!
Tripledemic Update
RSV continues, but we have yet to see any notable increases in flu or covid.
RSV-NET still shows an increase in hospitalizations nationally, ages 0-4 years shown in purple.
The FLUVIEW map is similar, though note this is tracking "influenza-like illness" which will be contaminated with other respiratory viral infections.
Biobot wastewater monitoring is at about the same level, still far below the January 2022 surge.
I continue to focus on wastewater data for SARS-CoV-2 due to the decrease and vast variability in tracking infections, hospitalizations, and deaths now compared to during the pandemic.
Autumn Thought
As I was finishing sweeping and raking leaves and carting them to the curb for pickup, a big wind came up. Within about 10 minutes, the areas I had just cleared looked exactly the same as before I started. The only change was that big maple tree outside my window now had significantly fewer leaves clinging to branches. At least I got a little exercise.
Langston Hughes, one of my 2 favorite American poets (Wallace Stevens being the other), wrote a short poem in 1921 entitled Autumn Thought:
Ever read Beowulf? Me neither. Nor do I plan to ever read this epic poem consisting of 3182 lines of alliterative verse. Recently I did read Grendel by John Gardner. Grendel is the monster who was killed by Beowulf in the famous poem. Gardner's book is told entirely from Grendel's perspective, very different from how Beowulf and the other humans saw things of course.
Malaria Season
Practicing in the Washington, DC, area for almost 40 years meant that I had a steady diet of malaria. Our "malaria season" was towards the end of summer when vacationing families returned home after visiting relatives in malaria-endemic countries. This seasonality abated a bit during the pandemic when international travel was scarce, then came back with a vengeance. Now, however, autochthonous malaria has been reported in Florida and Texas.
Autochthonous, from the Greek autokhthon meaning "sprung from the land itself," in this instance refers to malaria acquired without visiting a malaria-endemic country. I didn't mention the initial CDC report a couple weeks ago, but now that a second state is involved and CDC issued a health alert advisory, I'll attempt to summarize what's happening.
We still have virtually no clinical details about any of the 5 cases, but CDC implied they are all due to Plasmodium vivax which is not as severe/deadly as P. falciparum. Autochthonous malaria in the US was common in the old days, but since effective mosquito control programs in the 1950s it has been scarce. Prior to the current reports, we hadn't seen autochthonous malaria since 2003. High risk areas in the US are those that have high population density, plenty of Anopheles mosquitoes (including favorable conditions for their reproduction), and a source of people who have recently traveled from malaria-endemic areas. So, it's not surprising that Florida and Texas are points of origin now.
Speaking of mosquitoes, climate change has greatly increased the range of various insect vectors of disease; for example, Lyme disease risk has expanded geographically in recent years as deer ticks broaden their range. Anopheles mosquitoes are present in virtually the entire US.
For frontline providers, malaria shouldn't be the first thing to suspect in a child with fever in the US, but recognize that in cases of prolonged fever it is a consideration even without a history of international travel. Look at the CDC's malaria website for more details, and read this article if you want to see a longer discussion of (prepandemic) autochthonous malaria.
Foodborne Disease is Back
Another sign that the pandemic is lifting is this CDC report of 2022 data. Certain foodborne illnesses such as Shiga toxin-producing Escherichia coli, Yersinia, Vibrio, and Cyclospora infections increased compared to 2016–2018 data; Campylobacter, Salmonella, Shigella, and Listeria incidences didn't change much. Although they didn't show the data in this report, foodborne diseases decreased in the 2020-2021 time period.
I was a bit disappointed that, although the report did mention increased use of culture-independent diagnostic testing rather than culture, it did not mention the fact that the highly sensitive CIDT methods can be more prone to false positives. This makes it difficult to compare trends across time periods.
Ideally one would perform a backup culture test for bacterial pathogens particularly to detect antimicrobial resistance; CIDT can not test for this.
Can We Shorten Treatment Duration for Pediatric Urinary Tract Infection?
The short answer is yes, but the more difficult question is how to decide which patients are appropriate for shortened therapy. Even this randomized controlled trial couldn't answer that question. The study compared 5 versus 10 days of therapy for UTI in children 2 months to 10 years of age. Children who showed clinical improvement at 5 days treatment were then randomized to another 5 days of antibiotic versus placebo. Failure rate in the 10-day treatment group was 0.6% versus 4.2% in the 5-day group.
Ultimately I think the details of study design doomed this trial to leave this question mostly unanswered. In particular the duration of followup after stopping antibiotic was too short for the 10-day group (which would have skewed results to a falsely low failure rate). Fundamentally the problem with UTI treatment in children is trying to determine which children have pyelonephritis versus just cystitis, much more difficult in children than in adults. Pyelonephritis likely requires more than 5 days of treatment.
This study definitely adds to our understanding of pediatric UTI but I don't think is immediately transferrable to clinical practice. The accompanying editorial offers some ideas in this regard.
'Demic Doldrums
We continue to enjoy relief from covid from the standpoint of no evidence of major surges around the world, just continued pockets of upswings in disease activity (tempered by the knowledge that we aren't tracking it very well now). Of course, the number of total cases in this WHO graph, as of June 28, is pretty depressing overall.
According to WHO, confirmed covid deaths now number 6,947,192.
Blood Group and Covid
I have blood group A positive. Should I be worried? It's been known for a while that individuals with type A blood have a slightly higher risk of SARS-CoV-2 infection, and this recent article lends some credence to these observations by supplying a biologic explanation. The A blood group antigen is very attractive to the receptor binding domain of the virus, including omicron variants. But no, I'm not concerned. The increase in infection risk attributable to blood group is very small, paling in comparison to other risk factors.
Whatever Happened to Wastewater Monitoring?
In the US, wastewater monitoring for viruses like SARS-CoV-2 has great potential but is ineffective because it involves voluntary reporting by states. Most people in the US live in areas that don't monitor wastewater. Our northern neighbors in Canada, specifically Peel, Ontario, provide evidence that wastewater monitoring truly can be an early warning for increased infections. Investigators reported that wastewater levels predicted very reliably 1 day before the rise in infections and 4 days before a rise in hospitalizations during the omicron period of November 2021 to June 2022. At this point I'm not sure if the US has the resources to implement wastewater virus monitoring on a larger scale.
Better Evidence for MIS-C Treatment
The multi-system inflammatory syndrome in children is still difficult to diagnose precisely. Thankfully MIS-C seems less common in today's covid era with omicron dominance and high levels of antibody in the population. Now we have some better guidance for immunomodulatory therapy for MIS-C. This meta-analysis suggests that the combination of intravenous immunoglobulin plus glucocorticoid therapy improved cardiovascular dysfunction better than either agent alone. The study was very well done but had to rely heavily on nonrandomized cohort studies which introduces a great degree of bias in the results. We missed a chance by not conducting large RCTs of MIS-C treatment early in the pandemic.
Understanding Grendel
I needed to consult Wikipedia and other Cliff Notes-like versions of Beowulf to understand Gardner's book. As with everything I read, I think about what, if anything, might apply to me. With Grendel and Beowulf it was relatively easy. When faced with dramatically different perspectives, say for example pandemic deniers or anti-vaxxers (Grendel) versus traditional science and medicine (Beowulf), it's a good idea to try to see things from the opposing perspective. If one can do this without resorting to raised voices or worse, it's possible to have a meaningful dialog and even occasionally change minds, even my own! Next time you see me, look for Grendel perched on my shoulder. For those less prone to wild fantasies I recognize this is quite a stretch, but regular readers are accustomed to my tangents.
About 6 weeks ago, our washing machine's spin cycle started making noise and vibrations equivalent to the latest SpaceX rocket launch. After much hand-ringing and YouTube consulting, my wife and I decided it was time to move on from our elderly washer, initiating another round of internet searching. Our laundry space is very small. limiting our choice of washers. We ended up with a top-loading version equipped with a window in the top, making for some interesting entertainment better, than most of what's available on cable or streaming venues.
In the midst of all this upheaval, I somehow managed to keep an eye on infectious diseases.
Severe Neonatal Enteroviral Disease in France
In early May French authorities reported on several cases of severe enteroviral infections in neonates, summarized by the World Health Organization on May 31. Nine newborns developed late-onset sepsis syndromes with severe hepatitis and multi-organ involvement, resulting in 7 deaths. All had developed some symptoms by 7 days of age, typical of perinatal transmission from mothers. Cases were spread out since July 2022 and over 3 different regions but remarkably included 4 sets of twins.
ECHOvirus type 11 was detected in all 9 of the infants and in 4 of the 5 mothers tested. (A side note: I have capitalized ECHO because it is an acronym for Enteric Child Human Orphan. This came about because the original reports of ECHO viral isolation were from stool samples of human children; however, the children weren't orphans. Instead, it was the virus that was an orphan, because the children were asymptomatic. The virus was orphaned from any disease. This is a reminder that most enteroviral infections, even polio, are asymptomatic.)
Enteroviruses circulate worldwide all the time, with increases in the US usually in late summer. Enteroviral infection is always on the differential of neonatal sepsis syndromes.
Don't Work When You Are Sick
Easy to say, but in the past I've been guilty of toughing out a mild upper respiratory infection at work, trying to be diligent about hand washing, etc. Those days should be gone in our current covid era.
It's not surprising to see a new CDC report showing that a large number of foodborne illness outbreaks can be traced to sick restaurant workers. Almost 70% of 800 foodborne outbreaks reported to CDC from 2017-2019 had an identified etiology, and around 40% of those were traced to sick or infectious food workers. Norovirus was by far the most commonly identified at 47%, followed by Salmonella at 19%.
Handwashing, anyone?
Updated Hepatitis C Guidelines
We have updated hepatitis C management guidelines, including for children as young as 3 years of age. In pediatrics most of these cases will require subspecialty referral, but primary care providers should be aware of the key points. Thankfully, mother to child transmission of HCV is relatively uncommon, as I mentioned in my post last March 12.
Sonographic Testing in Febrile UTI
A group of investigators from Toronto and Ottawa, Ontario, Canada, performed a superb meta-analysis looking at the outcomes of obtaining renal ultrasound in children < 24 months of age at the time of first febrile UTI. I include it here because it demonstrates the most common outcome of a meta-analysis: no information that can be immediately incorporated into clinical practice.
The authors reviewed the varying guidance for when to obtain renal sonography in childhood UTI. The problem with sonography, in addition to the costs and inconvenience for families, primarily involve identification of trivial abnormalities that lead to unnecessary further tests and treatments, aka Ulysses Syndrome. I won't dwell at all on the complex statistical methods and only say that I was very impressed with the authors' thoughtfulness in constructing the approach.
Their initial literature search identified 2362 studies, culled down to 29 studies with an aggregate of 9170 subjects after applying predetermined study inclusion criteria. Nineteen of those studies were retrospective in design, with 10 involving prospective cohorts. None were randomized controlled trials or prospective comparisons of management strategies (e.g. comparing children who had sonogram after first febrile UTI versus obtaining after the second UTI). In this collection of studies, sonographic abnormalities were found in 22% of children. Most of these were clinically insignificant. In the 8 studies (2569 children total) that defined a population with clinically important abnormalities, the prevalence was 3.1% as seen in the forest plot below.
I include this figure to draw your attention to 2 things. First, look at the large variation in rates among the individual studies. Second, note the high numbers for heterogeneity. Heterogeneity refers to how different the designs of the individual studies were from one another, and high heterogeneity is a red flag for lower confidence in the results of a meta-analysis. It's sort of like a scale of comparing apples to apples (low heterogeneity) versus apples to oranges (high heterogeneity).
The end result of this study is a very clear roadmap for design of studies to decide if and when to perform renal ultrasonography in pediatric UTI. Most importantly, we must have prospective studies with comparison groups, to provide guidance to clinicians. The authors also highlighted the absence of any studies looking at parent-reported outcomes.
'Demic Doldrums
Last week saw a few noteworthy updates. CDC provided more information about covid transmission during the first in-person Epidemic Intelligence Service meeting since before the pandemic. In this meeting that occurred in late April, 1443 of 1800 in-person attendees responded to a CDC survey regarding covid infection. 181 (13%) tested positive, 49 received antiviral therapy, and thankfully none were hospitalized. 99.4% had received at least 1 vaccine dose prior to the conference.
An international group reported some success with a whole-blood transcriptional RNA "signature" to diagnose MIS-C. Using a discovery population of 38 children with MIS-C, 136 with Kawasaki Disease, 138 with viral infection, 188 with bacterial infection, and 134 healthy controls, they identified 5 genes to include in the signature. They then tested this in a validation study utilizing 37 MIS-C, 17 KD, 41 non-covid viral infections, 50 bacterial infections, and 24 healthy controls. They found reasonable correlations of the RNA signatures with the pre-established diagnoses, but of course the main problem is deciding whether the pre-established diagnoses were correct, i.e. we may not have a great gold standard for comparisons. I'll be watching closely for further studies on larger and more varied clinical populations.
The Washer Channel
Our laundry closet is microscopic, meaning we had few choices for what would fit in the space, not to mention our desire to have an ecologically sound machine. We ended up with an impeller model, new to us and therefore a source of curiosity. This week I finally finished watching the "Lucky Hank" series that I recorded and had mentioned in my April 23, 2023 post. It was interesting to see how Richard Ford's book was changed for the smallish screen. If you were thinking about watching "Lucky Hank," in my opinion you are better off reading the book, or even just watching your washing machine.
