pneumonia – Pediatric Infection Connection

March 11 marks the 5th anniversary of the World Health Organization declaring COVID-19 a pandemic. WHO had declared it a Public Health Emergency of International Concern (PHEIC) on January 30, 2020. I can't say I'll be celebrating this anniversary, but it did lead me to discover a new site: the CDC Museum COVID-19 Timeline. It's yet another rabbit hole for me to get lost in.

Wasteful Lab Tests

Two publications last week highlighted the developing science of diagnostic stewardship - increasing effective use of diagnostic tests and minimizing test ordering that does not help, or worse, harms, patients. First, a retrospective database study showed that respiratory pathogen panel (RPP) orders, already on the rise in pediatric hospitals, increased sharply during the pandemic but continue to be ordered at high levels even as the pandemic ended. The larger multiplex RPPs test for a number of pathogens for which there is no treatment and thus really no benefit to detecting those viruses for the vast majority of children. Also, most practitioners don't recognize that many respiratory pathogens (e.g. enteroviruses, adenoviruses, and Mycoplasma) can persist positive on these panels for weeks or months. largely because the pathogens themselves remain in our systems for a prolonged period though don't cause harm. Thus, positive tests can sometimes reflect something that happened 2 months ago and not have anything to do with the current illness being evaluated.

The authors found that respiratory testing overall seems to have remained quite high, at least through 2023, for both hospitalized children as well as for children seen in the ED but not hospitalized.

Not shown in a nice graph but included in the text of the article, they found that testing for SARS-CoV-2 alone decreased during the post-pandemic period, but this was not accompanied by a decrease in use of the larger RPPs. They also estimated the costs of such testing: about $20 million in 2016, a high of $111 million in 2022, and $83 million in 2023. Remember, this is just for children's hospitals included in a national consortium. The true excess costs likely are much higher.

Another report focused on a new guideline for management of pneumonia in neurologically-impaired hospitalized children, based on expert panel opinions of different scenarios. It's a useful guidance document, but what I found most interesting was in the diagnostic stewardship realm. They recommended against routine use of procalcitonin, ESR, CRP and large panel respiratory viral testing. (Sorry, you'll need to access the article to see all the explanatory footnotes, just too large to include here.)

The World

There's a lot going on in the world of infectious diseases outside of the US, and of course sometimes those issues come home to us via international travel - it's inevitable.

Sudan Virus in Uganda

In the latest WHO outbreak news from March 8, Sudan virus hemorrhagic fever continues to be a problem in Uganda with 12 confirmed and 2 probable cases total since the outbreak started in late January. That doesn't sound like much, but underreporting is always a particular problem in resource-poor regions. The most recent case had symptom onset in mid-February. We have no proven vaccines or therapeutic agents for Sudan virus disease, but WHO began a vaccine trial using a ring vaccination model: vaccinating primary and secondary contacts of index patients to see if this presents spread to the larger community. A therapeutic agent trial also is being planned.

Poliovirus in European Wastewater

Last week's MMWR (yes, it's back in mostly fine form!) announced findings of a vaccine-derived strain of poliovirus type 2 surging in wastewater in some European countries; this is the strain that has produced paralytic disease in other countries. The particular strain originated in Nigeria and has spread to 21 other African countries. There are no known cases of clinical infection, but remember that paralytic polio occurs in only around 1% of those infected with the virus and it's very difficult to identify the asymptomatic and mildly symptomatic infected people without very costly tools.

This isn't a time for alarm or for closing borders, though I'm sure some will use this as an excuse to do so, but it bears watching as well as ensuring adequate immunization against polio. Of course the killed polio vaccine, used in the US and other countries where polio has been eradicated, does not carry the risk of spread of vaccine-derived virus known to occur with the live virus polio vaccines.

Unknown Agent(s) Causing Deaths in Democratic Republic of the Congo

WHO officials have been monitoring this situation in the DRC, still very unclear whether it is a single agent or just a cluster of multiple known agents causing deaths. I haven't mentioned this previously because it is still unexplained and most often will not result in any new information concerning for spread outside of a limited region. I'll swing back with an update when the situation is pinpointed.

Measles

I'm saddened that measles likely will be a regular feature in my posts for the next few weeks at least. On Friday, CDC issued an advisory through its Health Alert Network about the increasing numbers of measles cases in Texas and New Mexico. These areas are definitely not on my travel list, even though I know my measles antibody titers are high. The advisory has a lot of useful information and links for healthcare providers and the general public.

I was also pleased to see that Texas has accepted help from the CDC, although I learned this only through lay press announcements that CDC had posted the news on X, absolutely the last place I'd normally go for any useful information.

I didn't bother to read any of the 491 replies, not a good use of my time.

Here's the latest from CDC; note that the recent decrease in numbers isn't necessarily real, there is a lag time for reporting and verification of cases:

The official CDC total for 2025 is up to 222 cases. One death of an adult in New Mexico who tested positive for measles is still under investigation to see if measles was actually the cause of death or just coincidental. Apparently this person did not seek medical attention before death.

As bad as the outbreak numbers are, I think I was most dismayed by the rumors in the lay press that CDC has announced a new study of a linkage between autism spectrum disorder and the MMR vaccine. This is perhaps the best-studied association known to modern science, with reports of cumulative numbers of several million children across the globe showing no connection between MMR and ASD. Yet another study seems like wasteful spending and use of government workers' time!

I won't bother to go into depth with the studies, you can look at the CDC site for an excellent discussion and some key references (click on the tab for references 3,4,5,6). However, I did want to make a couple points about issues that anti-vaccination proponents misinterpret or deliberately ignore. First, these studies look a large numbers of children who received and did not receive MMR vaccine and present results for the group as a whole. It is impossible to prove that MMR vaccine could not have caused a particular child's ASD. You can think of it as analogous to a situation where one tries to see if a particular medication had caused a rare side effect in a child where that side effect was not previously known to cause the adverse event. About the only way to prove it caused the problem for that child is to wait for the side effect to go away and then re-challenge the child with the same medication and see if the adverse event recurs. There's no way to do that with a vaccine and ASD. Second, anti-vaxxers often misinterpret how various tracking systems for vaccine adverse events are collected and what the limitations of these databases can be. From my observations of past RFK's interpretations of vaccine safety reports, I expect that any new study that doesn't align with his views that MMR causes ASD will just be disregarded or twisted to change the results. I pity the CDC scientists forced to work on the new study.

And, speaking of a waste of time, we now have a new CDC page listing all the conflicts of interest reports from ACIP members. I say this because the details have all been part of the public record and available at every ACIP meeting in the past, plus archived on the ACIP web site. I suspect this will be used as an excuse to remove members from the ACIP and replace them with less knowledgeable individuals who have never been involved with a vaccine trial.

All of this measles news caused me to unearth what's left of my old measles folder containing some very yellowed pages at this point. This coming week I'll go through some key articles on effect of vaccination rates on measles transmission, the reproductive numbers for measles, what we know about measles transmission in office settings (spoiler alert, it's not as much as you think), what vitamin A does and does not do for measles, and maybe some others. Stay tuned for my next post.

WRIS

At least we can end with some good news. The winter respiratory infection season continues to wind down, and without a big jump in covid so far. Both covid and RSV are low and decreasing; flu is still high but also continues to decrease.

That COVID Timeline Museum

Taking a stroll through the CDC's site wasn't that picturesque for me; in fact, there are no pictures or graphs beyond the same worn-out cartoon of the virus itself at the top. It did have a lot of words on a timeline, however, and I found myself trying to remember what was going through my mind at various times as the pandemic evolved. I wish I had kept a written journal, but I well recall that 5 years ago this month, among other concerns like grocery shopping, I was trying to research how to safely re-use N-95 masks in my clinical practice. We definitely had a shortage of those masks that prevented any single use options, and it was very time consuming to use other methods such as our hospital's limited supply of PAPRs (powered air-purifying respirators). US cases were still low in early March, 2020; here's a screenshot from the Museum:

We seem to have settled back into the good old days of infectious diseases and outbreaks, always something going on but at least nothing on the level of the past 3 years. Certainly we'll see an upswing in covid sometime in the coming months, but in the meantime I will try to return this blog to something approaching normality.

Short Antibiotic Course for Community-Acquired Pneumonia in Children

A group of Chinese investigators, working with McMaster University experts in evidence-based medicine, reported a meta-analysis looking at treatment duration in randomized controlled trials of antibiotics for pediatric CAP. Let me say from the start that this study is an excellent example of how to perform a high quality meta-analysis. I came to that conclusion before I realized that the McMaster group was involved, in particular Gordon Guyatt who is one of the world's leading researchers in EBM methodology.

The group defined short-term treatment as 5 days or less and found that shorter duration did not seem to alter outcomes compared to longer treatment. Here is one of the Forest plots looking at treatment failure of 3 or 5 days of antibiotics versus 5, 7, or 10 days:

This is one of many forest plots (also known as blobbograms, don't you love that!) including multiple subgroups that together provide reassurance for short-course therapy for CAP. The authors spent considerable time looking or sources of potential bias, somewhat difficult because each of the included studies had differing definitions and methodologies.

The children in these trials had relatively mild CAP, so the results shouldn't apply to those with more severe CAP. Also, It is likely that a large proportion of study subjects had viral infections. As the authors mention, "... it is usually extremely difficult to distinguish between viral and bacterial CAP." Still, the takeaway message should be to consider short (or no) antibiotic therapy for mild pediatric CAP.

Human Papillomavirus Transmission from Pregnant People to Their Neonates

Investigators from multiple Canadian institutions reported a prospective cohort of 1050 pregnant persons and their newborns with regard to HPV infection rates in the mothers, along with HPV detection in placentas and rates of positivity in their infants followed for a 6-month period. Note that the study recruited mothers early in pregnancy in the time period of 2010-2016. The bottom line was that 40%(!) of mothers had detectable vaginal HPV, but only 92/860 (10%) of tested placentas were positive. Detection of HPV from any site (conjunctival, oral, pharyngeal, genital) in newborns at birth or at 3 months of age was positive in about 7%, but no infant was positive at 6 months of age at any site.

This is a nice study and is somewhat reassuring that HPV transmission from mothers to infants in utero or perinatally is not a large problem. Of course, having seen innumerable infants with tracheal HPV, I can vouch that even an uncommon event like perinatal HPV transmission can result in severe consequences.

'Demic Doldrums

Please excuse my stretch to find an alliteration for this topic. Until we see the next covid wave, I liken this time to the doldrums. If you, like Jack Aubrey*, command a ship in the early 19th-century British Navy, the doldrums are to be feared; an absence of wind means your ship is stalled. It's not easy to row a 3-masted vessel in the ocean. However, a pandemic doldrum is a good thing. I'll include some 'demic doldrum postings as a semi-regular feature in upcoming blogs.

This past week had a few covid highlights worthy of mention. First, investigators at the University of Warsaw, Poland, reported 3- and 6-month echocardiographic evaluations in 172 consecutively diagnosed children with Multisystem Inflammatory Syndrome in Children. All of the subjects were asymptomatic from the time of their MIS-C hospital discharges. Results were quite good, even in those with initially severe cardiac involvement.

Along similar lines, we have some new data on safety of the Pfizer covid vaccine with numbers on myocarditis/pericarditis rates. It's a US commercial claims database analysis from the FDA and other organizations (but no contribution from Pfizer, so less chance of bias) and covers 3 million children 5-17 years of age. It looked at rates after both the primary series and after a third vaccine dose. Out of 20 different adverse events monitored, only myocarditis/pericarditis showed a safety signal but just in children in the 12-15 and 16-17 year age groups. The average rate for this complication was 39.4 events per million vaccine doses and tended to occur about a week after the primary series. The investigators were able to perform medical record reviews on only a subset of the events to verify diagnoses. This study is an example of the type of post-marketing data we need to continue to follow vaccine recipients for adverse events and is encouraging that nothing new is turning up so far.

We also have evidence of progress on the long covid front, more appropriately termed PostAcute Sequelae of COVID (PASC). We now have a better case definition. That may not sound like a big deal, but for something this complicated a good case definition is essential to figuring out diagnostic and management trial design and best strategies. A group from multiple institutions in the US developed a scoring system based on study of almost 10,000 adults. Signs and symptoms found to be significant enough to include in the scoring include postexertional malaise, fatigue, brain fog, dizziness, gastrointestinal symptoms, palpitations, changes in sexual desire or capacity, loss of or change in smell or taste, thirst, chronic cough, chest pain, and abnormal movements.

Meanwhile, it's time to pay attention to the southern hemisphere, just as we do for influenza, since it could be a harbinger for what we'll see in a few months. We don't have the same level of monitoring as early in the pandemic, but I will keep my eye on Australia, where cases are rising in almost all states though still at a low level.

Lastly on the covid front, variant studies such as those in the UK continue to show we are living in an XBB variant world. I'm also keeping my eye on a new one, EM.1.

*Jack Aubrey is the fictional British naval officer appearing in 20 (+1 uncompleted) novels by Patrick O'Brian. I've read all the books and was pleased to see the first in the series recommended for summer reading by the Washington Post's (and fellow Silver Spring resident) Michael Dirda. The books take a little work, a lot of unfamiliar terminology and details to get through, so not quite the easy beach read. You may be more familiar with the movie Master and Commander which was actually a combination of events from 3 of his books.

Whatever you're up to this summer, try to make room for curling up with a few good reads.

Tag: pneumonia

Happy 5th Anniversary