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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:

Flowers are happy in summer.

In autumn they die and are blown away.

            Dry and withered,

Their petals dance on the wind

Like little brown butterflies.

And... Happy End of Daylight Savings Time!

I've just returned from a wonderful family week at the beach to a steaming suburban DC and an annoying surprise at home. I'll just bask in my vacation afterglow and belatedly compose this post.

Bugs cont'd

I didn't think it was possible, but there are more mosquitos around my house now than before I left for vacation. Right on schedule, West Nile Virus infections are starting to heat up.

Hot off the presses, you can also add Texas to the list. Remember that although West Nile Virus is feared for its neurologic manifestations, most infections are either asymptomatic or result in a nonspecific febrile illness. The neurologic cases are the tip of the iceberg.

Hepatitis C - We're Missing the Mark in Public Awareness

A recent publication noted a big gap in delivery of care for hepatitis C, summarized below. I really like their cool poster-type depiction, check out the bottom line (at the bottom, of course).

Once again, our wonderful technologic advances in medicine are clouded by a failure to have them reach those who need them most.

More on Neonatal ECHOvirus Infections

The World Health Organization reported more cases of neonatal ECHO-11 infections in newborns, originally in France as discussed in these pages on June 4. Now WHO reports new cases from Croatia, Italy, Spain, Sweden, and the UK. No evidence so far that these events in different countries are connected; this might just reflect enhanced surveillance given the initial alert from France. The link above has a nice discussion of various aspects of the cases. Again, keep severe enteroviral disease in mind with any sick newborn in whom bacterial etiologies are not revealing.

'Demic Doldrums

Remember wastewater monitoring? It's not the greatest tool in the US due to the fact that monitoring is voluntary and leaves much of the US with no data. However, an epidemiologist at Johns Hopkins has been blogging on this and is predicting we are about to see an uptick in southern states. She admits the data are iffy, we'll know eventually if she is full of hot air or not.

Some interesting data appeared regarding maternal covid vaccination and newborn antibody levels. This was a small but well-studied group of 76 mothers who received an mRNA vaccine during pregnancy. Higher maternal antibody levels were seen in mothers who had systemic symptoms following the second vaccine dose, though all had good responses. Maternal transfer of IgG to infants was highest in those vaccinated in the second trimester. Breast milk IgG and IgA antibody to SARS-CoV-2 persisted about 5-6 months, just in time for the infants to start their own vaccine series! There were no significant adverse events in mothers or infants. Bottom line: since we don't know what covid will do in the future, pregnant persons would be well advised to get that new vaccine dose during their second trimester.

The US Government Accounting Office published some further recommendations for pandemic preparedness. I'm very glad these are appearing, but public interest and funding have cooled dramatically.

Also, I was pleased to see an analysis of journalistic coverage of preprint publication before and during the pandemic appearing (where else) but on the well-known preprint site BioRxiv. This coverage hit the boiling point during the pandemic but applied only to covid preprints, not to other scientific reports. Next up I hope we see some analysis of how many of those preprints never appeared in a peer-reviewed publication; some have attempted chart this already, but we probably need to wait another 2-3 years before passing judgement. I continue to worry that too much attention was focused on preprint postings during the pandemic; the blame for this is shared by journalists, scientists, and the universities and other organizations where the work was performed.

Lest we forget about flu, things aren't too bad worldwide but WHO did report some close-to-home hot spots in Costa Rica, Honduras, Nicaragua, and Panama.

My Astrologic Education

I always assumed the saying "dog days of summer" had something to do with a panting dog in the heat. I was barking up the wrong tree; now I've found out it originated with Hellinistic astrology. Officially, the dog days run from July 3 to August 11, according to the Farmer's Almanac.

I had a great time with my 3 sons and families at the beach, enough to keep me somewhat cool and calm after the thunderbolt of finding my air conditioner on the fritz when I returned home. Fortunately for my dog days, my house has 2 air conditioners. Until now, this was a complete mistake - our house could be handled by just one unit if only the ducts were all linked together. So, for now half the house is tolerable and I won't complain too much, at least until I get the bill from the air conditioning service.

Oh, and in case you haven't noticed, I've sprinkled weather- and temperature-related references and puns throughout this week's post. To keep your mind from sweating, see if you can find all of them. Answers in next week's post.

2

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.

National Liver Awareness Month isn't until October, but this past week saw a burst of activity around hepatitis concerns.

Eliminate Hepatitis C?

I'm having trouble understanding the details of President Biden's plan to eliminate hepatitis C in the US over the next 5 years; it's a nice idea, but it sounds impossible to me, especially in the setting of our country's current backlash against public health. The short explanation covered the basics of the proposal and seems sound, just very tough to implement. Remember, hepatitis C disproportionately affects communities with the greatest challenges to health care access.

The President's plan is completely focused on adults, but let's not forget about the children. Two studies by an international hepatitis C group appeared this week in Clinical Infectious Diseases and refined common wisdom about intrauterine/perinatal hepatitis C transmission.

It's important to note that both of these studies started at a time before availability of highly effective anti-HIV and anti-HCV therapy. The first article re-analyzed data from a prospective cohort of 1749 mother/infant pairs. The numbers are likely to be more accurate than previous studies because of the prospective nature and large size of the databases as well as utilizing more frequent testing. Vertical transmission, either in utero or at delivery, might be slightly higher than previously thought, about 7% in HIV-negative women and 12% in HIV-infected women. However, spontaneous clearance of infection by age 5 years in the infants was a bit higher than previously thought, which is good news and also will help inform any treatment protocols for children experiencing vertically-transmitted hepatitis C.

The authors also estimated, based on a separate analysis with a number of assumptions, that about 25% of infections occurred early in utero, 66% late in utero, and 9% at delivery. So, this lends support to current recommendations against using cesarean section to prevent newborn HCV infection.

The second article, by the same group, looked at a smaller number (179) of infected infants and further refined estimates. Most clearance of infection occurred within the first year of life. Any treatment regimen for infants likely should start after 3 years of age to avoid overtreatment of children who would clear on their own.

The accompanying editorial by Ravi Jhaveri is a longer summary than I presented here and is a good starting place for those who want to learn more, but unfortunately you need a journal subscription to view it.

Before leaving the topic of hepatitis C, let me also refer interested readers to the World Health Organization hepatitis C page. WHO goals for hepatitis C are a little different from US plans, though still steep: they propose elimination of hepatitis C as a public health threat by 2030. This endpoint is defined as a 90% decrease in new chronic infections and a 65% decrease in mortality using 2015 data as a baseline comparator.

New Hepatitis B Screening Guidelines

Also last week, CDC refined screening guidelines for hepatitis B in adults. It applies to individuals 18 years of age and older and better defines risk groups, but basically recommends screening everyone at least once. A nice accompaniment is a graph to aid interpretation of hepatitis B test results - something imprinted in my brain forever because I've had to explain it numerous times to students, trainees, and healthcare providers. It's complicated, but the graphs help.

Polio and Summer Vacations

Did you ever think we would need to worry about contracting polio on summer vacation? Welcome to the present. The increase in worldwide polio mostly is driven by infection with vaccine-derived strains from individuals who received live poliovirus vaccines that have not been used in the US since 2000; live polio vaccines are still used in some resource-poor countries. The US injectable inactivated polio vaccine is very effective, but those who are partially- or un-immunized are at risk to be infected with either live or vaccine-derived polio strains. CDC puts polio at a Level 2 concern for travelers, meaning to practice enhanced precautions. Their webpage lists areas with active polio. Now and through the summer is a good time to ask patients and families if they plan international travel and ensure immunizations are up to date. I know everyone is anxious to enjoy postponed summer travel, but we should all be careful.

In browsing other resources about polio, I came across an interesting campaign from Pakistan using "truck art" to help families overcome vaccine misconceptions and decide to immunize their children against polio. I'll leave you with this delightful image.