oseltamivir – Pediatric Infection Connection

Out of Chaos Comes Order

Bud WiedermannAugust 31, 2025August 30, 2025Leave a comment

It's not that I was expecting things to get better, but I didn't think we'd be seeing threats not only to the viability of the ACIP but now to the CDC itself. FDA and NIH also may be destined for near-irrelevance if current trends continue.

In the midst of this vaccine chaos, two more professional societies have stepped up. This past week the American College of Obstetricians and Gynecologists posted their recommendations for vaccination during pregnancy to include covid, influenza, and RSV. Unlike the AAP's recent recommendations (see last week's post), ACOG's referenced the Vaccine Integrity Project data and had an extensive bibliography. The recommendations are sound and should now be the preferred authority for vaccination during pregnancy. I hope the AAP will soon deliver a technical report for covid and RSV that incorporates VIP data.

Also, the American College of Cardiology published guidelines for adult immunization in the context of cardiovascular care. Vaccines covered are a bit broader, not only including covid, flu, and RSV but also pneumococcus and zoster. I also liked their table on FAQs from patients and suggested responses. Though the VIP data aren't mentioned (it did not focus on cardiovascular disease), the recommendations are sound and should be consulted when deciding on recommendations for adults with cardiovascular disease, including teenagers and young adults.

Who Can Receive a Covid Vaccine?

This is the biggest vaccine mess presently. At least the FDA updated its covid page last week. FDA revoked the emergency use authorization for the Pfizer vaccine for children under 5 years of age, not because of any new data but because they could. So, the Pfizer vaccine can only be used for pediatric patients starting at age 5 years, if they have a qualifying underlying condition. Those underlying conditions haven't changed recently and still appear in CDC's pediatric covid recommendations dated June 11, 2025. The Moderna vaccine is approved for use in children down to 6 months of age, but only with the presence of at least 1 high risk condition per FDA. Note that other entities have recognized that age 6-23 months is at higher risk for hospitalization, including ICU hospitalization. The Novavax vaccine is still approved starting at age 12 years, with the presence of at least 1 high-risk condition.

The FDA is requiring all 3 covid vaccine manufacturers to embark on new studies, throwing out previous immunogenicity studies which were used to approve minor strain changes in the vaccines, similar to flu vaccine changes each year. FDA is claiming (via executive fiat) that these now aren't good enough. The current FDA justification is: "First, the prior standard in CBER was acceptance of small immunogenicity studies using human sera, largely aimed at demonstrating numerical improvements in antibody formation against prevailing strains. These studies lacked formal statistical prespecification and power to test a clear scientific hypothesis. These studies were largely conducted, in CBER OCD’s opinion, to provide nominal justification for a strain change, even while there has been substantial uncertainty in whether such changes were necessary and/or beneficial. Moreover, these studies were not confined to the population of the current COVID-19 regulatory scheme, namely persons with 1+ risk factors for severe disease younger than age of 65 years and all those older than the age of 65 years." FDA will now require much larger randomized trials and also will require new trials to look at persistence of spike protein after vaccination (a rare occurrence at best, and likely less common than with infection itself) and a possible link to long covid. Mostly I see these new study requirements as a way to introduce even higher vaccine hesitance in the general population and to make it more expensive and difficult for vaccine manufacturers to continue covid vaccine production.

Healthcare providers have a lot to figure out in the coming weeks. First, how will ACIP's September meeting (now scheduled for September 18 and 19) alter covid vaccine recommendations? Second, how might practices and pharmacies be limited in administering covid vaccines, especially to children whose parents desire their healthy children to be vaccinated? Pharmacies in a few states are required by law to follow CDC guidelines only, and changing that requires changing state laws which could take time. Based on signals from the manufacturers, I expect the new mRNA vaccines, based on the LP.8.1 variant, to be available as early as next week.

Regardless of how this plays out in the next few weeks, practitioners need to be aware of the new FDA and ACIP recommendations as well as the more scientifically-based AAP recommendations. Also, the same issues as last year regarding dosing intervals for those needing a 2-dose regimen and the differences in dosage by age are still operative. A lot to swallow, but I expect more help from AAP and others as availability becomes clearer.

Clesrovimab for RSV Prevention

This week's MMWR summarized the outcomes of the June 2025 ACIP meeting that resulted in a recommendation to add clesrovimab as another option for RSV prevention in infants whose mothers did not receive RSV vaccine during pregnancy. It contains a lot of good information, here's an example of how to counsel mothers about choosing vaccination during pregnancy versus administering monoclonal antibody to their newborn infant:

Unfortunately, we're looking at an ominous turn that was signaled at the June ACIP meeting. Now one of the new ACIP members, an anti-vaccine proponent, is promoting ridiculous social media postings about safety of clesrovimab and also presuming it extends to nirsevimab. I think this may be a focus at September's ACIP meeting, with the ultimate goal of getting rid of monoclonal antibody prophylaxis for RSV in infants. I hope I'm wrong.

Bottom line, RSV prevention is indicated for all infants for their first RSV season, it is tremendously effective at preventing hospitalizations.

Chikungunya Vaccine Changes

Perhaps less of an issue as summer vacation season winds down, but I'm sort of getting whiplash with the back and forth of FDA consideration of the live chikungunya vaccine. There have been legitimate concerns about serious adverse events in older adults, including encephalitis in a vaccine recipient. On May 9 of this year, FDA issued a pause in administering this vaccine to those older than age 60. Then earlier this month, on August 6, that pause was lifted. Then on August 22 the license was completely suspended. I'm not sure what new information was available between August 6 and 22 other than a few more SAEs reported. I don't think it's necessarily wrong to take it off the market in the US, but the back and forth is a little unusual for the FDA of the old days. Fortunately another chikungunya vaccine is available and does not contain live virus, so US residents traveling to high risk areas have an alternative. I do see that the live viral vaccine is still available in Europe after a short pause. It will be interesting to see if they follow suit with the US.

Did We All Forget?

My August 17 post included an oseltamivir quiz - scenarios to determine willingness to prescribe antiviral treatment for influenza, based on national guidelines. I promised to include the answers in my August 24 post but I completely forgot. Apparently, since I didn't receive any messages about my omission, all of you forgot about it as well (or maybe just didn't care). Alas, you can't get off that easily. Here's a reminder of the outpatient scenario questions that were sent to variety of different pediatric providers.

1.a. A 6-year-old otherwise healthy male presents for a sick visit on his 2nd day of illness with cough, congestion, body aches, and intermittent fevers. In clinic he is afebrile, SpO2 98%, respiratory rate 24, and his lung exam is overall normal despite intermittent coughing fits. His rapid influenza test returns positive.

1.b. A 6-year-old otherwise healthy male presents for a sick visit on his 4th day of illness with cough, congestion, body aches, and intermittent fevers. In clinic he is afebrile, SpO2 98%, respiratory rate 24, and his lung exam is overall normal despite intermittent coughing fits. His rapid influenza test returns positive

2. An 8-year-old female with mild persistent asthma presents to the emergency department with 3 to 4 days of low-grade fevers and cough, now with 1 day of progressive shortness of breath and fast breathing at home. In triage she was found to be in moderate respiratory distress. She responds well to bronchodilators and steroids for her asthma exacerbation and is safe to discharge home. Prior to discharge her rapid influenza test returns positive.

3. A 10-month-old ex-full-term female is seen in urgent care for increased work of breathing. She is on day 5 of illness. She has mild respiratory distress that improves with suctioning, her SpO2 is 95% and respiratory rate is 36. She appears overall comfortable and well hydrated. Her rapid influenza test is positive.

4. A 1-year-old otherwise healthy female presents to urgent care for 2 days of vomiting and diarrhea. She has had slightly decreased oral intake and wet diapers. Her 5-year-old sibling has known influenza, and the infant’s rapid influenza test is also positive. In clinic, the infant is afebrile with stable vitals, well appearing, adequately hydrated, and has a benign respiratory and
abdominal exam.

According to various guidelines, all of these scenarios except one are indications to initiate oseltamivir therapy. The exception? It's vignette 1.b. above - the duration of illness is longer than recommended to initiate treatment in a healthy 6-year-old. What really interested me were the responses of the study participants. Participants who had managed the most cases of flu, i.e. the most experienced in the group, recommended oseltamivir the least frequently, only a third of the time. The general tone of the responses suggested to the study authors that practitioners are therapeutic nihilists when it comes to influenza treatment. However, we have fairly good evidence that oseltamivir is beneficial in influenza in many instances, avoiding medically-attended illness and shortening duration of symptoms. I'm generally a therapeutic nihilist, but show me the evidence and I'll change my tune as I have with oseltamivir for flu.

If you remember nothing else, know that if you don't plan on treating influenza with an antiviral agent in a particular patient, there is no point in testing for influenza. At least save money. Keep this in mind during our upcoming flu season.

I'm Not a Nihilist

Although I admitted I lean towards therapeutic nihilism unless evidence suggests otherwise, I'm not generally a nihilist about life. I realized this is a Debbie Downer post this week, ergo the quote at the top of this post attributed, not quite accurately, to the nihilist philosopher Friedrich Nietsche. The exact quote is in his 4-part tome Thus Spake (or Spoke) Zarathustra: "[O]ne must still have chaos in one, to give birth to a dancing star."

I never took a philosophy class and have never read anything by Nietsche except for the portion above. However, I am well versed in a variety other cultural matters, and I believe the correct source for the quote in the title is Mel Brooks. I hope that link provides enough cheer to counteract this downer post.

Do the Funky Chicken

Bud WiedermannAugust 17, 2025August 17, 2025Leave a comment

Last week I featured a John Prine song, Summer's End, that was pretty sad and mirrored my own feelings about all the chaos happening with health care policy in the US. A few days later after LSW (my long-suffering wife) had read the post, she told me the song brought tears to her eyes. I now feel a need to counteract that beautiful but downer song and video with a little silliness, ergo the Funky Chicken title. It arises from an epic quest my mechuten and I undertook during a family/clan gathering in Montana the past week. The goal of the quest: sighting the not-so-famous Chico Chicken.

But first, here's the week in pediatric infectious diseases.

Pediatric Tuberculosis in California

Most of the details in this article, like geographic distribution, will be useful only to practitioners in California, but it has some interesting take-home points for the rest of us. The authors mined a California TB registry database for the years 2000 - 2023 for individuals under the age of 25. Unfortunately over those years the types of data saved in the registry changed, so not all elements were available for all 24 years. The good news from the study was that TB rates fell over this time period; the unsurprising bad news was the tremendous ethnic and socioeconomic disparities of TB. Every infectious diseases physician knows that the most disadvantaged populations get the worst infections, with TB being a prime example.

Other study tidbits showed that birth outside the US was more prevalent in older individuals with TB.

While overall TB rates fell, central nervous system TB rates were relatively constant over the time period.

CNS TB accounted for almost half of the deaths from TB in children under 5 years of age. I know from long experience that TB meningitis and other tuberculous CNS infections can be very difficult to diagnose, leading to delays in initiating appropriate therapy and increased morbidity and mortality.

Towards Shortened Treatment for Acute Otitis Media

Initially I was pretty excited to see this quality improvement project to increase compliance with limiting AOM antibiotic treatment to 7 days for children 2-5 years of age without severe symptoms (T>39C, moderate to severe pain, or pain > 48 hours) and to 5-7 days for children 6 and older without severe symptoms. As I dug deeper into the manuscript, I realized it wasn't going to be that useful for the majority of primary care practice settings. It was based in a large "independent practice association of 80 privately owned pediatric practices with approximately 600 physicians, nurse practitioners, and physician assistants serving as pediatric primary care clinicians ... for approximately 350 000 children, with an annual visit volume of 1.4 million." The individual practices were as small as just one clinician, but still the interventions they made, mostly with EMR changes, wouldn't be possible in a smaller setting without shared EMR.

The QI study used standard methodology, including identifying key drivers of antibiotic decisions for AOM and a plan-do-study-act (PDSA) intervention, though just with 2 PDSA cycles. They found that a combination of educational intervention including sharing practitioner compliance numbers compared to the total group, plus embedding preconfigured order sets into their EMR, resulted in a modest improvement in appropriate AOM treatment for the older children without causing much of a backlash of too-short treatment for the kids under 2 years of age.

The criteria for appropriate antibiotic treatment were taken from a now antique AAP clinical practice guideline from 2013 that, among other things, recommends diagnosis of AOM using either pneumatic otoscopy or tympanometry. I don't know many frontline providers who perform those tests routinely for AOM, and this QI study didn't appear to provide any resources for accurate AOM diagnosis to practitioners.

What I really wanted to see but couldn't find was what the history and especially physical exam templates looked like in their EMR. Ideally these would include checkboxes for all the above severity factors plus more detailed checkboxes under the ear exam that would guide clinicians to best practices for diagnosis and serve to further automate the prescription choices.

And, I hope all the clinicians somehow were able to claim maintenance of board certification credit for their participation in this project!

Does Infection With a Common Respiratory Virus Protect Against Covid Infection?

I'll mention this study just briefly. It shouldn't change anyone's clinical practice, but it raises an interesting hypothesis that needs further study, i.e. that infection with human rhinovirus somehow protects against SARS-CoV-2 infection. The study was carried out during early phases of the pandemic, May 2020 to February 2021, in 12 US cities.

It's important to note that standard nasal swab respiratory pathogen panels detect many respiratory pathogens but utilize a combined human rhinovirus/enterovirus (HRV/EV) test that does not distinguish between the 2. The study investigators went a step further on a subset of swabs positive for HRV/EV to differentiate among the 2 virus groups and showed that 97.9% were HRV. Very few people were positive for other non-SARS-CoV-2 respiratory pathogens - remember, this was during a time period of school closures and lockdowns.

HRV infections were clearly much more common in children (in yellow) than in teenagers and adults in panel A.

However, panel B above shows no difference in SARS-CoV-2 infections by age, very different from panel A. Why aren't children, who are clearly being infected with HRV at higher rates than their elders, not also seen to have higher infection rates with SARS-CoV-2? The investigators posit that something about HRV infection is protective; they back this up partially by showing that children had higher rates of expression of putative SARS-CoV-2 protective genes that might be enhanced by HRV infection. We don't know if this extends to other respiratory infections because the others were so rare in this cohort.

As I said, so far this is just a hypothesis needing further testing, but it might have major ramifications for improvement of management and prevention of SARS-CoV-2 infection. Speaking of which ...

What's New With Covid?

Nothing much. Two key trends are still rising. Now I'm waiting with bated breath to see what covid vaccines might be available soon. FDA has approved one Moderna product for high-risk younger children, no movement on Pfizer products. FDA does not have another VRBPAC meeting on the schedule. ACIP still lists an August/September meeting, with dates TBA. I'm not aware of any scientific reason not to plan ahead for these meetings and suspect that political factors are at play.

More on Oseltamivir for Influenza

This is one instance where the editorial comment might be more helpful to clinicians than the study itself. The study basically provided further evidence for what we already knew: pediatric clinicians aren't following national guidelines for influenza treatment of children. The authors used responses from general practice, pediatric emergency medicine, and pediatric ID providers to 4 clinical vignettes. Unfortunately the response rate to the questionnaire was low, 452 out of 1124 (40%), which lessens the reliability of the results. Both inpatient and outpatient vignettes were studied. You might be interested in the outpatient vignettes themselves; there are 5 because the 2 variations for length of symptoms in the 6-year-olds were randomized for distribution. Respondents were asked to choose how likely or unlikely they were to recommend oseltamivir treatment for each scenario.

In next week's post I'll provide the "correct" choices based on the national guidelines.

The editorial summarizes succinctly the key issue - "do we need more evidence for influenza antivirals or do we need better awareness of and compliance with national guidelines?" If you have access to Pediatrics, it's worth a read in its entirety. It notes that it would be tough to perform a study to see if antiviral therapy for flu prevents hospitalization in children - it would require >100,000 participants. We do have good evidence from smaller studies and from meta-analyses that treatment lessens complications like pneumonia that could lead to hospitalization. We also have a lot of data about side effects, including the neuropsychiatric events I discussed in last week's post.

It's a confusing situation on the front lines of pediatric care during flu season. My own bias is that yes, we'd like to have perfect randomized controlled trials that give us answers, including about which subgroups of children benefit most from treatment and how late in the course of illness antivirals maintain effectiveness. Barring that, we need better education and implementation of our existing guidelines which would result in higher treatment rates and, most likely, fewer hospitalizations and days of school and work missed.

An Ultimately Successful Quest

Our recent family/clan event (LSW and I, our youngest son and his wife, and our son's wife's parents, her sister and her husband, and the sister's husband's parents - follow all that?) in Montana was centered around Bozeman and 2 smaller towns of Emigrant and West Yellowstone, as well as Yellowstone Park of course. We had a blast.

Through Atlas Obscura, one of my favorite travel sites, I discovered we were in the neighborhood of a 9-foot tall chicken statue of uncertain provenance, standing in the middle of nowhere. The directions weren't straightforward, and even after asking the souvenir shop workers at the nearby resort, mechuten and I still couldn't locate it after about an hour hiking in the hot sun. I thought my mechuten would quit speaking to me after this fiasco, but instead he became as obsessed as I was with finding the fiberglass fowl. We returned to the fateful area and this time got some more reliable advice from one of the horse stable guides. With a little further wandering, we rounded a corner and ....

So far, neither of us have developed signs or symptoms of bird flu. If you ever find yourself in this part of Montana, just check for directions in the horse stable; exact chicken coordinates are 45 degrees 20 minutes 45 seconds North and 110 degrees 41 minutes 55 seconds West.

I thought my life was complete after locating the cagey free-range Gallus gallus domesticus, but when I returned to Maryland I remembered some associated poultry musical and cinematic favorites. I hadn't heard Rufus Thomas's Do the Funky Chicken in ages. I had even forgotten a great verse:

"Oh, I'm feeling it now, I feel so unnecessary
This is the kind, this is the kind of stuff
To make you feel like you want to do something nasty
Like waste some chicken gravy on your white shirt
Right down front, here we go y'all"

I also remembered a scene from one of my favorite movies, The Blues Brothers, featuring Ray Charles along with Matt "Guitar" Murphy, "Blue" Lou Marini, Steve "The Colonel" Cropper, Donald "Duck" Dunn, Alan "Mr. Fabulous" Rubin, and Tom "Bones" Malone. Watch this if you want to know how to shake your tail feathers (at the 1:37 mark) and catch a couple of quick glimpses of some adorable kids (2:13-2:16 and 2:29-2:31).

If all this chicken craziness doesn't at least make you grin, you might want to seek professional help.

Summer’s End is Around the Bend

Bud WiedermannAugust 10, 2025August 10, 2025Leave a comment

I don't have kids at home, nor do I have different duties when the school year starts, but somehow I'm still sad to think that summer soon will come to a close.

It's not been the best of weeks for infectious diseases, highlighted by HHS cancelling $500 million worth of grants for mRNA vaccines based on completely faulty/bizarre reasoning by our HHS Secretary. Meanwhile, increases in emergency department visits and percent positivity of covid tests in many areas of the country suggest a covid bump is in process, just in time for start of the school year.

Scariest Journal Article in Recent Memory

Evidence is increasing that paper mills and other drivers of fraudulent scientific publications are a big problem. It ensnares all scientific fields; medicine and biology aren't immune. However, it's a slippery problem to define precisely given the newer advances in artificial intelligence. A professional field of "metascience" that examines scientific methodology and, increasingly, detects data falsification, has now become very important.

That scary article published last Monday comes from a group of metascientists at Northwestern University and the University of Sydney, Australia. I first heard about it through one of my favorite sources for tracking fraudulent publications, Retraction Watch. The article is scarier than [pick your scariest childhood movie ever, mine was the original 1958 version of The Blob starring a very young Steve McQueen] because of the massive scale of research fraud; it's going to be very difficult for some investigators to avoid referencing some of these fraudulent articles before they are retracted, if they ever are.

The authors of this study tried to get a better handle at this industrial-scale-sized research fraud whereby paper mills, for a price, will ensure an individual can publish multiple papers in scientific journals over a relatively short period of time, without ever lifting a finger to perform any research. This is far beyond the single unethical scientist fudging data or photographs to produce better results. I was fascinated to see how these authors approached the subject.

They performed various standard literature search techniques but focused on a few areas that lent themselves well to tracking falsifications. Some journals, such as PLOS ONE and journals in the Hindawi group, make it easy to access article content and metadata and also publish the names of the individual who edited (reviewed) the manuscript for publication. This allowed the metascientists to look for trends in individual editors and journals. Also, I learned about the Academic Research and Development Association (ARDA). The name sounds impressive, but actually it's an organization anyone can use to find journals or conferences that guarantee publication, generally without regard to content.

I won't delve deeply into the methodology, in part because it is very complicated and certainly not for the faint of heart. However, please note that PLOS ONE and Hindawi journals are thought to be of high quality overall and were used here because they were very transparent in their editorial processes. It makes it even scarier to see how quality journals can be hijacked. Here are a few things I learned.

The investigators discovered 22 editors (in red below) who accepted articles that were subsequently retracted significantly more frequently, as a percentage of total articles they reviewed, than would be expected by chance alone.

Keep in mind that the y axis is a log scale. Also, the number of articles handled by these flagged editors were on the high side, which may be a reflection of the fact that many journals allow authors to suggest reviewers (editors) to assess their manuscripts. Paper mills can funnel articles to editors they know will accept anything for publication.

Want more? I learned a new term, "journal hopping." Paper mills need to guarantee publication for those willing to pay, but over time a particular journal may become less desirable, e.g. because it loses indexing in key literature search engines, or just goes out of business. Paper mills need to keep ahead of these changes, ergo journal hopping. The metascientists found that journals listed by ARDA are deindexed at a much higher rate than those not listed. As an example, 13 of 39 (33.3%) of Scopus-indexed journals listed by ARDA in 2020 were deindexed later, versus 147 of 27,197 (0.5%) journals not indexed by ARDA over the same time period. They also listed some amazing examples of ARDA journal fraud, such as an article about roasting chestnuts published in a journal focusing on HIV/AIDS care and an article about malware detection that found a home in a special education journal.

The number of retracted articles in scientific journals has been increasing exponentially (note again the log scale on the y axis) recently, driven mostly by paper mills.

The article has many more scary examples that I won't elaborate on further. The authors point out that, in order to limit paper mill impact on scientific discourse, a lot of things need to change in how research fraud is detected, investigated, and sanctioned, especially taking care to remove such monitoring from those with potential conflicts of interest. The practice of financial rewarding reviewers for rapid publication and for increasing journal impact factors (a worthless metric that encourages fraud, IMHO) must end. Research institutions should not be left to investigate their own scientists. Also, if this is really such a wide-scale fraud enterprise, leaving fraud detection to a small group of (mostly) volunteer metascientists would be overwhelming. We need a redo of our systems, and quickly.

If you're looking for a bottom line to take away from this article, look no further than its title: "The entities enabling scientific fraud at scale are large, resilient, and growing rapidly."

When Did You Last Treat a Case of Bubonic Plague?

Well, for me, never. It isn't that common in the US, and I've never practiced near an endemic area. Treatment traditionally has been with parenteral antibiotic therapy, often with aminoglycosides, but quinolones do have activity against Yersinia pestis. Now we have a new study from Madagascar that included a lot of children and provides some reassurance for using oral quinolone therapy monotherapy for bubonic plague. It was an open label randomized non-inferiority trial comparing oral ciprofloxacin for 10 days to initial 3 days of parenteral aminoglycoside (streptomycin or gentamicin) followed by 7 days of oral ciprofloxacin. The results did show noninferiority for the primary day 11 endpoint of death, fever, development of secondary pneumonic plague, or receipt of alternative or additional treatment for plague up to and including day 11.

Secondary endpoints included reduction of bubo size of less than 25%, and the ciprofloxacin monotherapy group did have a higher rate of failure at 46.8% compared to 36% in the aminoglycoside-ciprofloxacin group. This did not meet noninferiority criteria, though the clinical significance of this endpoint is open to question.

Plague is on the list of bioterrorism agents, so I have always kept up with new developments in the field even though I've never seen, and probably never will see, a human case.

Neuropsychiatric Events With Oseltamivir Treatment of Flu

I've been puzzled by prior reports of serious neuropsychiatric side effects from oseltamivir during influenza treatment; most seemed to have come from other countries, and there wasn't much about this in the US, including in my own experience and that of my colleagues. Now we have reassurance that oseltamivir likely isn't to blame for these events. The study is a retrospective cohort of children 5 - 17 years of age enrolled in Tennessee Medicaid from July 1, 2016 to June 30, 2020. They ended up with almost 700,000 children enrolled. Oseltamivir treatment was associated with lower rates of neuropsychiatric events compared to no treatment. "The outcome definition includes both neurologic events (seizures, encephalitis, altered mental status, ataxia or movement disorders, vision changes, dizziness, headache, sleeping disorders) and psychiatric events (suicidal or self harm behaviors, mood disorders, psychosis or hallucination)."

The authors performed a large number of sensitivity analyses for various confounding variables, and the findings remained robust. Oseltamivir does have side effects, particularly minor GI disturbances, but the study design and available data did not include other potential side effects.

Management of Congenital CMV Infection: Start With Mom

CMV is the most common congenital infection, averaging about 1 in 200 newborns in the US and even higher in certain socioeconomic groups. Most are asymptomatic at birth but may develop hearing loss and neurodevelopmental disabilities later. Many experts have advocated routine screening of all newborns for congenital CMV infection, but these researchers in France provide early screening of pregnant people. Hot off the presses (August 9) is information on antibody avidity, amniotic fluid PCR sampling, and maternal treatment with valacyclovir starting in the first trimester of pregnancy.

Most primary care pediatric care providers probably don't remember that antibody avidity, the degree to which IgG antibody "sticks" or is bound to the antigen (CMV in this case) varies with stage of infection. As a general rule of thumb, a finding of high avidity antibody binding excludes recent (within 3-4 months) infection, while low affinity antibody binding cannot exclude recent infection.

Pregnant women seen at one French center from 2012 to 2024 all were offered CMV IgG and IgM testing in the first trimester of pregnancy. Those with positive IgG and positive or equivocal IgM were then tested for IgG antibody affinity. Fetal infection was defined as a positive CMV PCR on amniotic fluid, with amniocentesis performed starting at 17 weeks gestation. The study inclusion criteria were those who had positive IgG, positive or equivocal IgM, low IgG antibody avidity values, and a positive amniotic fluid CMV PCR. Starting in 2019 at this center, women thought to have primary CMV infection in the first trimester were offered valacyclovir prophylaxis while awaiting confirmation by amniotic fluid PCR. That's all pretty confusing, here's a study flow chart that might explain it better. (Liaison and Vidas are two different commercially available avidity assays.)

I'll show just one of many outcome figures, looking at vertical transmission of CMV by timing of maternal primary infection and whether the mother received antiviral treatment or not.

This study didn't really discuss its limitations, but one always needs to be careful about making sweeping conclusions from retrospective studies which have multiple confounding factors compared to prospective randomized controlled trials. These confounders are basically impossible to predict reliably. Also, CMV serologic assays aren't perfect, always tough to rely on these, but it's the best we can do. The study did add substantially to our understanding of reliability of the 2 avidity assays. The data from this study support early treatment of pregnant people with primary CMV infection in the first trimester to prevent fetal infection. Some states in the US now routinely screen newborns for CMV, and perhaps one day we'll see combination early screening of pregnant people plus of their newborns at birth in the hopes of decreasing congenital CMV infection and identifying infected infants sooner so that further evaluation can guide earlier treatment.

Missing John Prine

Some music lovers would have recognized the title of this week's post as part of the lyrics from a song, Summer's End, from the last album released before he died from covid in 2020. I can't multitask when listening to Prine, his lyrics are too thoughtful for me to let go as background noise.

Tag: oseltamivir