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.
I could read the study - but easier to ask you !
These days virtually all children have had prenatal ultrasounds - did any of the studies indicate how often a post UTI ultrasound differed from reported prenatal scan ? And then , how many of these differences were clinically actionable ?
Great question, but the meta-analysis didn't really look at prenatal imaging at all. I don't know if any of the original articles included had presented data on this. As the article itself states, prenatal imaging may capture renal anomalies and thus lowering the likelihood of finding something significant in that newborn postnatally (but of course not zero).