mycoplasma – Pediatric Infection Connection

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.

Yes, the winter respiratory illness season has ramped up in the US. Predictably, so has the hype. I even saw a term, "white lung syndrome," tossed out. It's a completely inappropriate description especially when one considers the main lower respiratory disease agent circulating now is a mild one, Mycoplasma pneumoniae.

Before we dive into winter respiratory pathogens, let's touch on a few other noteworthy events from the past week.

Watch Out for Cantaloupes (and many other foods)

CDC announced a new Salmonella outbreak alert this past week, covering 34 states and resulting in over 60 hospitalizations so far. Be particularly cautious of pre-cut cantaloupe products. Perhaps more revealing, however, is the fact that we have 2 other Salmonella outbreaks being monitored now (dry dog food and fresh diced onions) plus 4 others that have ended recently (backyard poultry, raw cookie dough, ground beef, and small turtles). Salmonellosis can mostly be avoided by knowing about high risk situations (e.g. poultry, ground meats, reptiles, poorly washed raw foods) and practicing good handwashing, food washing, and cooking thoroughly, as well as by refrigerating leftovers promptly.

WHO World Malaria Report

WHO released its annual report, and it's no surprise we are behind schedule for decreasing malaria cases worldwide. It's a very long, detailed report even allowing for the fact that some details appear in a few different languages. Some key details:

Rapid detection assays have been very helpful in diagnosing Plasmodium falciparum infections in particular, but new mutations in the histidine-rich protein 2 gene may allow these organisms to escape detection.
As always, resistance to antimalarials is spreading, requiring ongoing monitoring.
Not to be outdone by the pathogen, the vectors (mosquitoes) are increasingly becoming resistant to insecticides. This has led to new recommendations for mosquito netting in malaria-endemic countries.
And last, but not least, climate change. Here's a direct quote: "WHO has declared climate change to be the single greatest threat facing humanity."

I liked this graphic for visualizing malaria case distribution geographically.

More Concern for Invasive Group A Streptococcus

The Pan American Health Organism just issued a new alert for iGAS infections in Argentina. This joins a growing list of reports in a number of countries, primarily in Europe. Research is pointing to new M1 mutations with toxin production that might confer increased virulence.

Winter Respiratory Illness Season

Clearly I need to switch from calling this a winter respiratory viral season to a winter respiratory illness season; not all the pathogens are viruses, and of particular note is M. pneumoniae, a free-living organism in the class called Mollicutes. Technically they are bacteria, but they lack a cell wall and I think it's a bit misleading to the general public to refer to them as bacteria. Nonetheless, they aren't viruses. The organism is very difficult to grow in culture, requiring special media and expertise as well as 1-3 weeks incubation, but now it is included in most multiplex respiratory pathogen panels so easier to diagnose. Serologic diagnosis is fraught with false positives, about the least useful serologic testing for human disease that I know of.

"Fried egg" image of M. pneumoniae in culture:

One important thing to know about mycoplasma disease is that it is endemic everywhere, but epidemics occur about every 3 to 7 years and last anywhere from 1 to 2.5 years. I've witnessed this myself several times in my practice in the DC area, and it appears that a new mycoplasma epidemic partially explains the larger numbers of respiratory diseases in Denmark (you may need Google translate) and the Netherlands.

Perhaps more importantly, it's been very difficult to show that antimicrobial treatment has any benefit for illness caused by M. pneumoniae, which is clearly a self-limited infection. Probably if treatment has a benefit it would need to be initiated very early in the disease course. Testing for the organism requires a relatively expensive multiplex PCR assay and probably isn't worthwhile to test for the usually mild "walking pneumonia" version of the infection.

By far the biggest hype in the lay press (and from some congressmen) is the surge in respiratory illness in China, especially in northern regions. However, we do have some reassurance from the WHO taken from review of Chinese reports (Google translate again helps somewhat here). It appears that what is going on is simply an increase in known respiratory pathogens, rather than a new pathogen that China is hiding from us. I can add anecdotally that, as I track reports in real time and compare to the December 2019/January 2020 tracking I was doing, this looks nothing like the new appearance we saw with SARS-CoV-2. That doesn't mean there isn't something new circulating at low levels, but certainly no cause for alarm or to call for travel restrictions.

Remember that China only emerged from their "zero covid" lockdown a year ago, so this is their first full winter respiratory season with most children having no experience with any of these respiratory pathogens the past 4 years. As we saw in the US last winter, this likely produces a temporary situation resulting in increased numbers of cases and increased disease severity.

On the sort of good news side of covid, CDC reported benefits of covid vaccination for children 6 months to 4 years of age from a very recent time period covering July 2022 through September 2023. Vaccine effectiveness (receipt of at least 2 vaccine doses) for preventing acute care visit or hospitalization was 40%, though with a large confidence interval due to the relatively small numbers of events. The somewhat downer side of the report was that only 10% of the 7400+ children in the study had actually received > 2 vaccine doses.

Moving on from covid, RSV activity in RSV-NET is taking off, it is now full-blown RSV season.

Flu is heating up in more parts of the country, but not widespread yet.

Covid also is increasing, and now CDC has a better display for wastewater tracking:

The above is current for the week ending November 25 and predicts we will see a winter increase in covid illness. This is supported by a slight increase in positivity rate in covid testing in CDC data. However, you can see most of the recent uptick in positivity rate is being driven by influenza and RSV. If wastewater is truly predictive, we'll see the covid curve start to rise more dramatically in the coming weeks.

A Chuckle to Share

I loved this brief blurb in the November 20 issue of The New Yorker (I'm way behind in my magazine reading, blame Thanksgiving holidays). Every parent (and grandparent) will identify with this fictional list of communications from a nursery school to parents, announcing outbreaks of lice, pink eye, smallpox, "pirate's gastroenteritis," and rinderpest.

I Didn't Forget Diego Rivera

Last week I challenged you to name the organisms depicted in various Diego Rivera murals as collected in a recent article. According to the authors, figure A represents Salmonella typhi, though that seems a stretch to me. Figure B is easier, it looks a lot like the Gram negative intracellular diplococci seen with gonorrhea. Figure C shows spirochetes, mostly likely syphilis, but D is vague again, some sort of Gram positive intracellular cocci. Take your pick.

Tag: mycoplasma

The Wiedermann Thanksgiving Massacree of 199?