tuberculosis – Pediatric Infection Connection

Quite an eventful week! In general, I try to keep politics out of my commentary, though I fell short of this goal in my February 25, 2024, post where I blasted the Surgeon General of Florida; that may be the only time I've singled out an individual in a negative manner in this blog. Now, I find that his name is being mentioned as the next Secretary of Health and Human Services. All of this reminded me of an almost 300-year-old pamphlet.

But first a bit of the other health news from last week.

Mayaro Virus

In spite of my voracious appetite for medical knowledge, the list of viruses I've never heard of is lengthy. Now my list is one item shorter due to a new report. Mayaro virus is another of the arthropod-transmitted alphaviruses prevalent in parts of South America, causing a febrile illness with severe arthralgias very similar to its cousin Chikungunya virus. Primates serve as a reservoir with the primary vector the mosquito Haemagogus janthinomys. If like me you are a bit shaky on some elements of South American geography and history, Suriname is a former Dutch colony located just north of Brazil and has territorial disputes (in light green) with neighboring countries.

Measles in Vietnam

Vietnam is introducing earlier measles vaccines to try to stem an epidemic. In this WHO Western Pacific region report, you can see Vietnam is going the wrong way in measles incidence. Like the rest of the world, we all "enjoyed" a pandemic period where many traditional infectious diseases transmitted by respiratory routes showed significant declines due to non-pharmaceutical interventions, only to now reappear in greater numbers. For measles, Vietnam showed an incidence of 7.4/million population in 2020, dropping to 0.3 in 2022 but now back up to 7.1/million in 2024.

Normally Vietnam recommends measles immunization at 9 months of age, but now this is being dropped to 6 months due to an increase in cases in younger age groups. (You'll need Google translate for this link.)

Computerized Radiograph Interpretation for TB?

Although this study was performed only in adults, I thought it was worth mentioning as a possible glimpse of the future. Investigators in Africa and southeast Asia looked at the performance of a computer program to interpret chest radiographs in about 1400 adults with cough > 2 weeks in duration and found the program to have significantly higher sensitivity than a relatively new blood test for host response gene activation in TB as well as superior to CRP. When trying to diagnose TB in resource-poor settings that may not have access to good molecular and other microbiologic methods for TB diagnosis, we need every tool available. I'll be interested to see how newer methods for TB diagnosis evolve.

More on Bird Flu

CDC reported that 7% of 115 dairy workers at farms known to have infected cows showed serologic evidence of influenza A H5N1 infection. Four of the 8 seropositive workers did not recall having any respiratory signs or symptoms since the cows were first noted to be sick. This rate wasn't terribly different from the 60% of those with no illness history in the seronegative group. Given that H5N1 so far seems to be a mild illness in humans, the finding of asymptomatic infection isn't surprising. Clearly we need a lot more data on human illness in these and other settings.

Benefits of Quadrivalent Meningococcal Vaccine

Of our recommended vaccines, meningococcal vaccine probably has the lowest "return on investment." Meningococcal disease is relatively rare but comes with very high morbidity and mortality when it does occur. This modeling study estimated the number of cases of invasive meningococcal disease in 11-23 year-olds prevented by vaccination during the period 2005-2021. One always needs to take modeling studies with a grain of salt because they by necessity make a lot of assumptions. The authors did a good job of trying to look at all possibilities. They concluded that "vaccination averted an estimated 16 (95% CrI, 8-31) deaths among adolescents aged 11 to 15 years and 38 (95% CrI, 19-75) deaths among those aged 16 to 23 years." I guess those are small numbers when compared to the entire US population, but this is still a meaningful benefit.

WRIS

Things are still relatively quiet, though with regional variations.

I did happen to note that wastewater levels of RSV are very high in Maryland, so maybe that will be the first pathogen to increase in my region.

Make America Healthy Again

I feel like the MAHA acronym was one of the nicer-sounding political slogans to appear recently. However, the fact that it was popularized by a notorious pseudo-science fringer concerns me for what might lie behind MAHA. That made me recall a short treatise by Jonathan Swift (of Gulliver's Travels fame) that I came across a long time ago. I read it again a few times this week, and this highly satirical essay entitled "A Modest Proposal" is worth 10 or 15 minutes of your time. I think it is best read without knowing where the narrator is going, so I'll give you a SPOILER ALERT. You can read the original document in the link now, before reading what I write below, or you can just forego the surprise and keep on with my take below.

The narrator beings with an "objective" view of the problem, in 18th century Ireland, of the economic woes of a large section of the populace. He particularly hones in on the difficulties that parents in lower economic strata have in providing for their children. After going through some numbers assumptions that we can only guess at the accuracy, he decides that Ireland has about 120,000 children born to impoverished parents annually. How can the country solve this problem? He offers his modest proposal, or "humble solution:" It's a sudden turn in tone, to say the least.

"I have been assured by a very knowing American of my acquaintance in London, that a young healthy child well nursed, is, at a year old, a most delicious nourishing and wholesome food, whether stewed, roasted, baked, or boiled; and I make no doubt that it will equally serve in a fricasee, or a ragoust."

Yes, Mr. Swift in his satirical essay is proposing cannibalism as a solution to poor families trying to raise their children. He goes on to describe various details of preparation and serving.

MAHA sounds OK now, but I fear of this becoming another modest proposal. I'll withhold my judgment until we see more details of the plan.

We continue forward into winter respiratory illness season, and I find myself wondering again how it will compare to prepandemic winter seasons. At that time, my annual wish had been that influenza and RSV peak activity would not coincide; if they did, healthcare facilities faced an overload. Now, covid is thrown into that same mix. Furthermore, in the prepandemic winter school breaks that occurred in the midst of flu season often seemed to put a pause in flu transmission that carried over into January. In today's world of infectious diseases, will this still be true, or could the increased travel and crowding result in a spike of respiratory infections? Perhaps we'll know in another month.

Bad Omen for Mpox?

Last week CDC released a Health Alert Network post about a new outbreak of mpox in the Democratic Republic of Congo (DRC). Although it is happening in a country far away from the US and not a common travel destination, I believe it's worth taking note of. It could impact health around the world, including in the US. To me this is more noteworthy than the respiratory illness surge in China that I mentioned last week because it may impact the US directly. The current DRC outbreak is a different clade of mpox that is potentially more virulent and could spread worldwide. We all remember the 2022-23 outbreak resulting in mpox becoming endemic in the US and a particular hazard for men who have sex with men.

The previous outbreak was caused by clade 2 mpox, generally endemic in western Africa. The new DRC outbreak is clade 1 that historically has been more common in central Africa and may cause more serious infections generally including higher mortality. What is different in the DRC now is that human to human transmission has been documented, included sexually-transmitted disease. So far clade 1 has not been seen in the US, and the alert mentions that none of the 150 US isolates from 2023 undergoing testing (a 12% sampling) have been clade 1. It is likely that the same countermeasures that have been effective for the clade 2 outbreak, including vaccine and antiviral therapy such as tecovirimat, brincidofovir, and vaccinia immune globulin, will be effective for clade 1 disease. Now is a good time for healthcare providers to brush up on clinical diagnosis of mpox and counsel high risk individuals to seek vaccination.

Remember Eleanor

For most of my career I have kept and updated a list of Bud's Laws, now a compilation of 10 aphorisms designed to trigger recall of some key bits of medical knowledge for clinicians. One of them is "Remember Eleanor" to trigger the fact that tuberculosis has many clinical presentations, some outside of the usual fever, pneumonia scenario. The Eleanor in the aphorism refers to Eleanor Roosevelt who died of tuberculosis in the 1960s. Her physicians had been treating her for aplastic anemia; TB was finally diagnosed when it was too late for treatment to be effective (plus she apparently had drug-resistant TB!). Whether her physicians actually misdiagnosed her aplastic anemia or the steroids they administered for that just reactivated latent TB isn't clear to me.

A recent MMWR report of neonatal death following failure to diagnose mother with active TB is a heartbreaker. Mother did have risk factors for tuberculosis and concerning symptoms of insufficient weight gain and hyperemesis dismissed as due to pregnancy, plus chronic cough written off as gastroesophageal reflux. Mother wasn't evaluated for TB until her newborn became seriously ill in the third week of life, ultimately developing septic shock and dying at 6 weeks of age.

TB diagnosis is always easier in retrospect; please keep it in mind especially for individuals with risk factors.

Respiratory Virus Tracking

Clearly CDC is messing with me. Their cutoff for weekly data summary is Friday, but they don't post the updates until the following Monday. So, my blog post on Sunday will be a week off.

Still, nothing is going to change too much in a week to alter clinical practice during winter respiratory illness season. Here's a few details from the latest CDC graphics.

Remember that the graphic above will capture other illnesses besides flu, but it's a pretty good indicator for flu season. RSV hospitalizations in the 0 - 4 year age group still appears to be rising nationally.

Percent positivity of RSV tests may have peaked already, too early to be certain but that could be a good sign.

Covid wastewater levels continue to be high and rising.

Note that you can visit this site and see a breakdown by regions of the country; currently the Midwest has the highest levels.

Managing Mild Pneumonia in Children

I welcome comments to this blog and I answer them routinely - unfortunately subscribers don't get an email notice when I do so, you'll need to keep track of comments when you are looking at the site.

This past week I received a comment from Dr. Rebecca Carlisle who practices mostly in a pediatric urgent care setting. I thought it was worth answering in a regular post because it brings up an issue I think most pediatric practitioners are facing now. She wrote, "I’ve been seeing a lot of kids-ages 4 to young adults with terrible sounding lungs-wheezing/rales-not really responding to nebs. I’ve been chalking it up to “viral pna” but a couple times have started Azithro (one of my least favorite medicines bec I think it’s overused in the adult population).... Your post mentions that tx doesn’t usually help, but maybe in early illness? Any elaboration on that and should I be trying more Azithro, never Azithro?"

It would be great if we had a guideline that helps us with managing pediatric community acquired pneumonia (CAP). Of course we did have one from the Infectious Diseases Society of America, but it was written in 2011 and has been archived, meaning it is no longer accurate. They are working on a new guideline, too late to help us now. WHO also has a guideline but that is geared for managing CAP in resource-poor countries and not that helpful for a US population.

Regardless of whether we have current guidelines or not, probably the most important consideration in management of mild CAP in children is knowing what pathogens are circulating in your community. In the midst of flu season. rapid testing for influenza should be obtained if treatment is considered, whether it be for mycoplasma, other bacteria, or influenza. Azithromycin likely is still the drug of choice in this age group, given that mycoplasma is more common in the slightly older child and it may have some activity against pneumococcus, depending on local resistance patterns.

The real problem with azithromycin in this circumstance is that it may have little to no effect on the course of mycoplasma lower respiratory disease. Randomized placebo-controlled trials in children from decades ago showed no difference between erythromycin treatment and placebo outcomes. A 2015 Cochrane review reinforced this: "In most studies, clinical response did not differ between children randomised to a macrolide antibiotic and children randomised to a non‐macrolide antibiotic. In one controlled study (of children with recurrent respiratory infections, whose acute LRTI was associated with Mycoplasma, Chlamydia or both, by polymerase chain reaction and/or paired sera) 100% of children treated with azithromycin had clinical resolution of their illness compared to 77% not treated with azithromycin at one month." The authors called for high-quality RCTs to answer the question, but the problem is that, since mycoplasma LRTI is self-limited, the sample size needed for a definitive study is quite large, probably prohibitively expensive unless a pharmaceutical company comes out with a new macrolide where future sales might warrant investment in such a trial.

For now, chest radiographs aren't indicated for mild pediatric CAP, and diagnostic testing should be limited to treatable infections such as influenza or for situations where elderly or immunosuppressed close contacts could benefit from knowledge of the child's infection. Azithromycin treatment of mild CAP in the school-aged child probably should be the exception rather than the rule. It's not a never event, just something to be considered based on the child/family individual concerns. Just my opinion.

TB in Literature

Speaking of Eleanor, probably your holiday vacation reading list isn't full of books about TB, not a particularly uplifting topic. My favorite TB novel by far is Thomas Mann's The Magic Mountain, but it does require a bit of diligence to make it through. If you're interested in a shorter novel where TB is featured, think about Penelope Fitzgerald's The Blue Flower. Her other 8 novels are all great as well.

Tag: tuberculosis

A Modest Proposal