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Tag: nirsevimab

Published on Leave a comment on Settling Into Winter

I'd been spared from most snow shoveling due to mild winters the past few years. Fortunately, this week I discovered that my outdated acetaminophen still seems to work.

Artificial Intelligence for Pediatric Infectious Disease Diagnosis

Investigators at Baylor College of Medicine (bias alert: my alma mater) developed an interesting method to distinguish the covid-associated Multisystem Inflammatory Syndrome in Children (MIS-C) from endemic typhus, the latter enjoying a bit of a resurgence in south Texas. The rest of us don't have reason very often to consider these 2 entities together since endemic typhus (aka murine or flea-borne typhus) is pretty rare in the US beyond southern California, southern Texas, and Hawaii. However, the results from this preliminary study serve as a proof-of-concept model for other diseases. The methodology is very complex, to say the least. Briefly, they looked at electronic medical record data over a 2-year period for anyone being tested for Rickettsia typhi, the etiologic agent for endemic typhus, or having a rheumatology consult request for MIS-C. All of the typhus-positive patients and a subset of MIS-C patients were included in a preliminary dataset for the AI modeling. A large number of patient variables were tested in an iterative process to come up with a preliminary scoring system which was then validated on another MIS-C patient set. The final scoring system included 15 variables: age of patient, duration of fever, height of fever, highest heart rate, neutrophil to lymphocyte ratio, AST, ALT, sodium, troponin, BNP, fibrinogen, epidemiologic link to COVID-19 case, antecedent illness, conjunctivitis, and rash. The authors claimed their scoring system correctly classified all 220 patients in their training dataset (100% accuracy) and was 99% accurate in the 160-patient MIS-C cohort used as the validation dataset. Of course we still need further evidence that this works well in other settings and institutions. I hope the AI and machine learning process itself, so far published only as a preprint, can be applied to other clinical situations.

Another Tick-borne Virus

Speaking of vector-borne infections, now researchers in China report a novel virus from the Nairoviridae family was found to be a cause of febrile illness in 26 of 252 febrile patients tested in northeastern China. They named it XCV (Xue-Cheng Virus) after the geographic site. (IMHO, I wish we could get away from naming diseases according to a geographic site, it just encourages xenophobia.) They also found evidence that XCV caused cytopathic effect in vitro and was present in 3-6% of ticks in the area. They authors don't provide much clinical information about the cases, and a link to a supplementary appendix didn't contain any more details. Overall it does appear this is a new infectious pathogen.

If you never heard of nairoviruses, don't feel bad. Some infectious diseases physicians may be aware that Crimean-Congo hemorrhagic fever virus is the main human pathogen in this family.

Chronic Wasting Disease

I don't think I've ever mentioned CWD in these pages previously. It is a fatal neurodegenerative disease seen in cervids (deer, elk, moose, reindeer) and caused by an infectious prion. I've been watching reports about spread of CWD in the US and across the globe for many years. I mention it now because of the publication of a new report from CIDRAP concerning for potential for spillover into other species, including humans, similar to what has happened in humans with Creutzfeld-Jakob Disease, kuru, and bovine spongiform encephalopathy (mad cow disease). Here's the North American distribution of CWD.

CWD has been expanding in numbers and in geographic areas in the US the past 20 years, increasing the possibility of spillover into humans. The CWD prion can remain intact in the environment for years, and prions are not inactivated by cooking infected meat.

The report maps out several recommendations for monitoring this situation; the recommendations bullet list alone takes up 5 pages of the 102-page document. It's a good example of how to plan proactively, but of course implementation takes funding of public health endeavors.

Venison steak, anyone?

Good News in the Vaccine Department

Three quick comments on recent vaccine studies.

First, I was somewhat surprised to see a pretty good uptake of RSV prevention modalities for pregnant people and infants. In the 2023-24 RSV season in the Kaiser Permanente Northern California system, around 75% of at risk infants received protection either by maternal vaccination or nirsevimab administration after birth.

I'm hoping it is even better this season. Remember that Kaiser is a health system very well designed to deliver high rates of vaccinations and other preventive interventions to its subscribers. However, individual private medical practices can and should aim to achieve high rates of RSV prevention.

Another study provided more evidence that it is safe to administer 2-month vaccinations to hospitalized preterm infants. It was a randomized controlled trial of preterm (<33 weeks gestation) infants hospitalized at 3 NICUs and eligible for vaccination at 6 - 12 weeks of age. 223 babies were randomized to receive either 2-month vaccines or no vaccine and then monitored for 48 hours. The unvaccinated group of course could receive vaccines after this 2-day period. Although apnea was more common in the vaccinated group, it didn't appear to have any adverse effects.

The vaccines administered were PCV13, DTaP, HBV, IPV, and Hib.

The last vaccine study I'll mention is another estimate of flu vaccine effectiveness last year. Specifically, it looked at outpatients at least 8 months of age in 7 states that were part of a flu VE surveillance system. The target endpoint was outpatient visits with positive influenza testing. VE against any influenza illness was 41% (95% Confidence Interval [CI]: 32 to 49): 28% (95% CI: 13 to 40) against influenza A(H1N1)pdm09, 68% (95% CI: 59 to 76) against B/Victoria, and 30% (95% CI: 9 to 47) against A(H3N2). Protection was found in all age groups except for the 50-64-year-old group. Differences in age groups (and also related to influenza A subtypes) likely are related to imprinting, i.e. what flu strains people are exposed to early in life, but this study wasn't designed to answer this question.

WRIS

As we roll along in the winter respiratory infection season it's worth taking a look at where we are. CDC has some newer data for the "big 3" viruses in pictorial form. (See https://www.cdc.gov/flu-burden/php/data-vis/2024-2025.html, https://www.cdc.gov/rsv/php/surveillance/burden-estimates.html?ACSTrackingID=USCDC_2067-DM142871&ACSTrackingLabel=CDC%20Updates%20%7C%20New%20In-Season%20Estimates%20of%20COVID-19%20and%20RSV%20-%201%2F7%2F2024&deliveryName=USCDC_2067-DM142871, and https://www.cdc.gov/covid/php/surveillance/burden-estimates.html?ACSTrackingID=USCDC_2067-DM142871&ACSTrackingLabel=CDC%20Updates%20%7C%20New%20In-Season%20Estimates%20of%20COVID-19%20and%20RSV%20-%201%2F7%2F2024&deliveryName=USCDC_2067-DM142871.)

Note that the influenza numbers include 2 weeks longer than for RSV and covid. I did a quick calculation of death rates per illnesses for each, using the midpoint of the ranges: influenza 1.3 deaths/1000 illnesses, RSV 2.5, and covid 3.1. Of course these are all ballpark estimations but still show that infections with any of the big 3 are worth preventing.

Here's the most recent look from FluView, which captures respiratory illnesses other than influenza.

Still hoping that flu and RSV reach their peaks before covid ramps up.

Español en la Nieve

My shoveling activities were greatly enhanced by one of my new neighbors, a 3-year-old boy who just moved here from Colombia and only speaks Spanish. I'm forever embarrassed by the fact that the Spanish I've retained from my south Texas childhood can't be used in polite company, but my new friend was speaking his native tongue to me while we shoveled together. The upside if we have a heavy snow winter in Maryland is that I may develop new Spanish fluency!

Published on Leave a comment on Is It or Isn’t It?

The Democratic Republic of Congo has been back in the news, this time not for mpox but for a mystery illness in an isolated, rural region of the country. Varying numbers of fatalities have been noted, but solid facts are sorely lacking. I am reminded of how early outbreak news percolates and changes; odds are low but not zero that this is a serious, new pathogen. Meanwhile, we can discuss several new publications that are on more solid scientific footing.

Vaccine Effectiveness Updates

Two manuscripts accepted for publication provided new information on VE measurements, one concerning influenza and the other looking at covid vaccines in young children.

CDC, along with other investigators, published an analysis of influenza VE for the 2023-24 flu season. For that year, the vaccine strains were well-matched for what eventually circulated in the US. The most common strain circulating was A H5N1pdm2009. Looking just at the pediatric population, VE in preventing hospitalizations and urgent care/ED visits was very good in all age groups as shown below: 58% for both outcomes overall, though with a wider confidence interval for hospitalizations since these were less common events.

The covid vaccine article is quite complex, involving investigators at multiple sites and listing 35 identified authors! Sadly it doesn't have any nice tables/figures that allow a short summary. I see 2 categories of take-home messages from the data: 1) as always, VE depends on which outcome you're looking at; 2) covid vaccines aren't that effective at preventing infection, but do help significantly in preventing complications of infection.

This multi-center study is actually a grouping of 3 cohorts (total 614 subjects) of children who had longitudinally-collected data including weekly sampling during the period of omicron variant circulation, 9/19/22 - 4/30/23. Variants were verified by genetic sequencing of about half the strains. Antibody studies and history questionnaires at study entry were utilized to determine evidence of prior infection. Here are the numbers from the study:

  1. Children with prior infection had less chance of both infection and symptomatic infection than did those without prior infection: Hazard Ratio [HR]: 0.28 [95%CI: 0.16-0.49] and HR: 0.21 [95%CI: 0.08-0.54. This was true regardless of timing of prior infection.
  2. Children with prior infection AND vaccination also had lower hazard ratios: HR: 0.31 [95%CI: 0.13-0.77], compared to those who were unvaccinated with no prior infection.
  3. The one slightly unique finding in this study is as follows: "There was no difference in risk of infection or symptomatic COVID-19 by vaccination status alone, regardless of timing of vaccination or manufacturer type. However, naïve participants vaccinated with Pfizer-BioNTech were more likely to be infected and experience symptomatic COVID-19 compared to naïve and unvaccinated participants (HR: 2.59 [95%CI: 1.27-5.28]), whereas participants with evidence of prior infection and who were vaccinated with Pfizer-BioNTech were less likely to be infected (HR: 0.22 [95%CI: 0.05-0.95])." In other words, vaccination didn't do very well at preventing infection.

This study is very complex but also very rigorous; I can't do it justice in a small summary. The major limitation is the relatively low sample size, meaning that the investigators couldn't do much in the way of subgroup analysis to try to look at other variables. Relatively few children received the bivalent Pfizer vaccine, so it's very hard to interpret specific differences between Pfizer and Moderna vaccines. Also, the small sample size precluded any assessment of complication risks following natural infection, one of the big advantages for being vaccinated.

Does Nirsevimab Prevent Other Infections Besides RSV?

According to another new study, the answer is "sort of." Investigators looked at around 3000 infants randomized 2:1 to receive either nirsevimab or placebo and then followed with respiratory swab PCR testing. The pictorial bottom line:

Not mentioned in the pictorial summary is that the cumulative incidence of rhinovirus/enterovirus coinfections was lower in the nirsevimab group, leading to my "sort of" conclusion.

The important bottom line of the study, however, is that no replacement infections appeared. Replacement infections refer to the concern that once an infectious agent is greatly reduced by preventive measures, another pathogen will take its place, lessening the impact of the preventive measure. This was a concern for Hib vaccine early on, but no other meningitic pathogens arose. Later, the same concern arose for pneumococcal vaccination. There is evidence that replacement pneumococcal serotypes started to become more common, but the overall rates of pneumococcal infections still declined significantly. This is why we're still trying to add other pneumococcal serotypes to newer conjugate vaccines.

Parvovirus and Myocarditis

Last week I mentioned the reports about increase in parvovirus infections likely spurred by non-pharmaceutical measures to prevent respiratory pathogen spread during the pandemic. A spinoff of this kind of surge can be a surge in complications of these pathogens. I was intrigued by this report from Italy about parvoviral myocarditis, which is a slightly controversial topic. Etiology of viral myocarditis is difficult to determine without myocardial biopsy, and parvovirus myocarditis is particularly suspect because of older reports of parvoviral detection in cardiac tissue from individuals who never had concern for myocarditis. So, for an individual patient, it's hard to be certain of a parvoviral etiology for myocarditis even with a positive tissue biopsy. This post-pandemic surge may help clarify the situation.

Europe in general seemed to have an earlier surge in parvovirus infection than we did in the US, possibly because pandemic restrictions were lessened earlier there. Here is a breakdown of the Italian report by age and timing.

And a breakdown of how the diagnosis was made. Only 2 were with myocardial biopsy; blood PCR can persist positive for a long time after parvoviral infection. IgM serology always is suspect due to nonspecific factors. A matched control group without myocarditis to see rates of parvovirus IgM and blood PCR positivity would have been helpful.

Of course I'm hoping we don't see a surge of myocarditis cases soon. If cases do spike, it will be particularly tough to figure out if it happens during a covid surge.

Mycoplasma Complications Too?

Along similar lines, a study from Texas suggests that the Mycoplasma pneumoniae surge might be associated with a greater risk of complications. This is a retrospective review from a single institution documenting an increase in M. pneumoniae infections seen below the shaded section.

It's important to recognize, as the authors do, that this is a cohort skewed towards inpatients who had multiplex PCR testing. Also, mycoplasma PCR can persist positive for many weeks after infection (as do live organisms), so a positive PCR doesn't conclusively mean that the current illness is caused by mycoplasma. What was important and of some concern in the report is that 13 of the 41 children hospitalized with respiratory symptoms required ICU care. They also described 16 children with RIME (Reactive Infectious Mucocutaneous Eruption) with one of those children requiring ICU admission.

Avian Flu Updates

The news media (sometimes breathlessly) relayed new findings that a single mutation in influenza A H5N1 strains could increase adherence to human respiratory epithelium, increasing chances for greater infection rates in humans. I haven't yet bought into this panic.

Keep in mind that single mutations don't necessarily occur in isolation; often multiple mutations occur, some increasing virulence while others resulting in lower virulence. This in vitro study is an important contribution to our understanding of how avian flu might evolve and most importantly supports the need for close tracking of this agent in all animals, including humans.

Along those lines, I was please to hear that the US Department of Agriculture will implement mandatory milk testing nationwide for A H5N1. Previously this has been mostly a voluntary effort in the US. We still need much more monitoring for this agent in order to prepare for potential increase in human cases. Let's hope funding will be available to support these efforts.

WRIS

The winter respiratory infection season has begun, at least for RSV. We are now officially at moderate activity nationwide.

Influenza is increasing slowly with A H3N2 the most common subtype. COVID-19 projections are increasing, though not yet a big bump in clinical illness.

WHO to Help in the DRC

I figure I've been watching various feeds for outbreak alerts for about 30 years, starting with the ProMED service that still sends me at least a daily update. So, I've had early looks at these events, but also a slew of false alarms of new diseases that turned out to be mini-outbreaks of previously well-described illnesses. The latter are far more common than newly emerging infectious agents. So, I'm both watching closely but not overly concerned about the cluster of respiratory illnesses with significant mortality being reported from Kwango province (outlined in red) in rural southwestern DRC, bordering Angola.

Early reports suggest a predilection for children. The rural location with lack of medical facilities hinders any investigation. Also, this type of region, with close proximity of humans to many animal species, provides the potential for infectious agents to jump to other animal hosts. It appears the region now has appropriate support from WHO, and I would expect to hear more definitive information within the next several days, maybe in time for an update in my next post.

I guess the rural location is also a silver lining, with less risk for worldwide spread if this is in fact a new disease. I'll go out on a limb using past unknown outbreak experience and predict this won't be a new pathogen. Here's hoping.

Published on Leave a comment on Welcome to Our 10th Month!

The first of the month happens to fall on a Sunday, the day I put together my weekly post. I am transiently aware that the root word for December derives from the number 10 yet persists as the name of what is now our 12th month. Having nothing better to do while trying to digest my Thanksgiving excess of wonderful food, I decided to refresh my memory as to how this rather bizarre nomenclature has persisted.

Meanwhile, the CDC had a nice Thanksgiving recess and thus will not have any new updates on the winter respiratory infection activity until December 2. I can only report anecdotally that RSV season is in full swing in the Washington, DC, metropolitan area, with little in the way of influenza or covid cases. Still, there is lots to talk about from last week.

A Rare Mention of Early Phase Studies

I don't often mention results from phase 1 or phase 2 human trials; the studies are important but the findings aren't immediately transferable to clinical practice. Generally we need to wait for phase 3 trials to be completed so that we know how effective the intervention is likely to be. However, I couldn't hold myself back from these 2 reports because of the novel approaches and the likelihood that they represent what the future will look like.

The first report is of bacteriophage therapy for infections caused by multiply-resistant bacteria. Clinicians may recall that bacteriophages are viruses that exclusively infect bacterial cells and can destroy them. Bacteriophage use for treating infections resistant to all known antibiotics isn't new, it's being used by most tertiary medical institutions for the past few years at least. It requires painstaking hunting for a bacteriophage that is effective for the particular patient's infecting bacterium. What was enlightening to me was how CRISPR technology was used in this phase 2 trial to custom-design a bacteriophage, in this case for use in E. coli urinary tract infections. The resulting product is, unlike classical therapeutic bacteriophages, independent of the infecting organism's susceptibility pattern and can be used off-the-shelf, eliminating a patient-specific and very expensive, cumbersome, time-consuming search for an effective phage. Note, however, this still is a fairly cumbersome therapy. The actual treatment consisted of 2 days of intraurethral and 3 days of intravenous phage therapy, plus oral trimethoprim-sulfamethoxazole. The subjects were all adults and numbers were small, but relatively good responses were seen in the treatment groups.

A second part of the phase 2 trial is underway and one hopes we will see further results from this trial.

The other preliminary study is a phase 1 trial of a diphtheria antitoxin (DAT) developed as a monoclonal antibody. Currently DAT is an equine antibody and is in short supply worldwide. Having a ready supply of human monoclonal antibody could alleviate the shortage plus reduce the allergic reactions related to use of horse serum. In 41 adult subjects in this trial, the monoclonal product produced higher neutralizing antibody concentrations than that seen with the equine DAT and strongly suggests that it will be highly effective. Needless to say in our rapidly-advancing anti-vaccination environment, this could be an important advancement not just in resource-poor countries but also in the United States as well.

Tonsillectomy for PFAPA

Periodic Fever, Aphthous stomatitis, Pharyngitis, and cervical Adenopathy syndrome has been one of the dilemmas of my clinical practice for decades. It is likely a genetic periodic fever syndrome, but no precise gene mutation has yet been identified and thus there is no definitive diagnostic test available. PFAPA eventually resolves spontaneously with no known clinical sequelae. If all of the clinical components are present, the diagnosis is fairly easy, but likely there are variants of this syndrome, including those presenting with periodic fever alone. Tonsillectomy was effective in a randomized controlled trial but usually is employed only after other, simpler, therapies fail. Now we have an observational study on long-term (median 8.8 years) follow-up of 86 children in Sweden who underwent tonsillectomy for PFAPA. Entry criteria required periodic fever with at least 1 other finding of aphthous stomatitis, cervical lymphadenitis, or pharyngitis as part of their usual symptom complex. Here's the bottom line in (not pumpkin) pie format:

This information will be helpful in discussing treatment options, but it should be noted that, because this is a genetic disease that could have multiple gene variants, results may not be applicable to other populations beyond this Swedish cohort. The authors did not report the subjects' racial or ethnic backgrounds.

Parvovirus B19

Last week the CDC gave us a bolus of reports on parvovirus infections in MMWR. In a study of clinical and donor plasma testing in 2024, the percentage of samples showing positive parvo B19 antibody and/or PCR showed a significant jump. Below are the results for PCR testing of blood donor plasma.

In addition to the above, this MMWR issue also had 2 other parvo B19 reports focusing on high risk populations. Aplastic crises in sickle cell disease patients showed an upswing in an Atlanta children's healthcare organization:

Another report focusing on pregnant people in Minnesota this year showed increases across younger age groups:

Five laboratory-confirmed infections occurred in pregnant people at 13 - 20 weeks gestation, with the following characteristics:

Perhaps this is all part of the "immunity debt" catch-up we are seeing in so many infections occurring post-pandemic. Pregnant people often are infected by their own school-aged children. A good time for clinicians to brush up on parvovirus B19.

Cost Effectiveness of RSV Prevention

I've discussed how covid vaccination recommendations vary by country, such as the UK restricting vaccination of lower-risk groups due to cost concerns even though being vaccinated has lower risk of sequelae than with natural infection in these groups. Now we have some numbers for RSV prevention through maternal vaccination or with administration of monoclonal antibody to infants, courtesy of 2 CDC-funded analyses.

For maternal immunization during weeks 32-36 gestation, incorporating various estimates of newborn outcomes and maternal side effects from vaccination, vaccination of mothers year-round cost $396 280 per quality-adjusted life-year (QALY) saved. If vaccination were limited to the September through January period, the cost dropped to $163 513 per QALY saved. Changing various inputs to the model resulted in ranges from a net cost savings up to $800 000 per QALY saved.

For infant nirsevimab utilization using similar analyses and looking at single RSV season benefits in infants 0 - 7 months and 8 - 19 months of age, assuming half the US birth cohort received nirsevimab, cost savings were $153 517 per QALY saved. "Nirsevimab in the second season for children facing a 10-fold higher risk of hospitalization would cost $308 468 per QALY saved. Sensitivity analyses showed RSV hospitalization costs, nirsevimab cost, and QALYs lost from RSV disease were the most influential parameters with cost-effectiveness ratios between cost-saving and $323 788 per QALY saved."

Clearly the costs to society vary widely depending on what assumptions are made for effectiveness, outcome rates, and costs of product and hospitalizations, etc. As noted in the accompanying editorial, these costs are so high because the products themselves are very expensive, much more so than our other vaccines. If nirsevimab were to cost $50 instead of almost $500 per dose this would certainly be a net savings to society, but don't hold your breath for the cost to decrease anytime soon. Still, both of these products have very high clinical effectiveness, and pediatric healthcare providers should provide nirsevimab to all eligible infants whose mothers did not receive RSV vaccine during pregnancy.

Hiding in Plain Sight

Somewhere buried in the back of my mind is the fact that the word December contains the Latin root for 10, decem. This dates back to about 750 BCE and the calendar of Romulus, the first king of Rome. The calendar had only 10 months, starting with March and ending with December, with some sort of in-between period that became January and February during the reign of the next king, Numa Pompilius, who took over in 715 BCE. Various rearrangements appeared over the next few centuries. What I should have known but didn't, September, October, and November kept their names derived from the Latin names for numbers 7, 8, and 9. So, we're stuck with outdated names for 4 of our months that date back to use during a brief 50-year period occurring almost 3 centuries ago.

Also, I'd be remiss if I didn't report back to you about the Wiedermann Thanskgiving Massacree of 2024; thankfully, there was none. The most amazing thing that happened was that for the first time in modern history, not quite dating back to Romulus, I didn't make a written minute-by-minute oven and stove schedule for Thanksgiving day. Such activity was rendered moot largely because the 3 primary cooks (my sister-in-law, my wife, and me) were too organized from the start. It was a breeze, except for a brief cursing episode by yours truly when a new bird-carving technique proved to be less than desirable.

Happy 10th Month.

Published on Leave a comment on Meh

I had expected last week's ACIP meeting to include more presentations and discussions about which covid strain to include in our fall vaccine. I viewed only a small portion of the meeting live (darn those pesky patient care issues!), so I probably missed any brief mention of strains; the slides themselves didn't address strain selection, other than to go with the FDA's statement for use of JN.1 lineage with preference for KP.2 if possible. I still found some interesting details about covid and nirsevimab and will share those with you. Perhaps meh is a bit of a harsh judgement, but I love the word.

In the meantime, thankfully still not much going on in the pediatric infectious diseases world this summer.

Love That New Technology

The CRISPR technology has been in the news for a long time. In case you had forgotten, like I did, it stands for Clustered Regularly Interspaced Short Palindromic Repeats and is now reported to have high sensitivity and specificity for detecting antiviral drug resistance and influenza subtype rapidly enough to be used as a point-of-need assay. The study itself requires journal subscription (thank you, GWU faculty status) to read in full. Investigators studied influenza isolates from the 2020-21 season looking primarily at AH1N1 and AH3N2 strains. The report is highly technical, beyond my ability to critique the laboratory methods, but the take-home message is important: if such a method is scalable (e.g. cheap enough) to employ across the world, including in resource-poor communities, it would be a boon to early warnings of resistant and/or new flu strains. I'm keeping my fingers crossed.

I must applaud scientists in this realm for their acronym constructions: in addition to CRISPR and others, they also used DETECTR (DNA endonuclease-targeted CRISPR trans reporter) and SHERLOCK (Specific High-sensitivity Enzymatic Reporter unLOCKing) assays. Elementary, my dear Watson. (And, that phrase never appeared in any of Arthur Conan Doyle's writings!)

Dengue HAN

Perfect timing after my mention of dengue last week, the CDC issued a Health Alert Network warning about dengue in the US. According to the Pan American Health Organization, early signs are that cases in the Americas this year will exceed last year's numbers, a year that was already much higher than previous years. Here's an example from the report of what's going on in the Caribbean subregion:

Puerto Rico is under a healthcare emergency because of dengue, and we will certainly have cases of autochthonous (acquired in the US without travel to an endemic area) transmission in the mainland US again this year, primarily in Florida and other southern states. The HAN is worth reading.

This would be a good time to review clinical presentations of dengue and be prepared to investigate/obtain consultation for suspected cases.

Pustules and Vesicles in Afebrile Infants <60 Days of Age

Pediatrics had a nice retrospective review of 183 infants from 6 academic hospital-based pediatric dermatology practices. It's open access and has a nice suggested management algorithm.

Note the first branch in the algorithm details key features to decide whether HSV evaluation and treatment is recommended.

ACIP Meeting Highlights

The regular meeting was spread over 3 days last week. Slides are posted, and I picked out a few that contained interesting new information.

First, even with all the problems of supply chain and late administration, nirsevimab appears to have been incredibly effective in preventing RSV hospitalizations and healthcare visits.

Yes, that's about 98% effectiveness in preventing hospitalization, with very narrow confidence intervals. When this slide was shown it elicited a round of applause from the committee members. This is truly remarkable. Similar results were seen using a different RSV surveillance method. Both the above and below slides are from the Payne presentation on June 28.

It appears we'll have better availability of nirsevimab for the next RSV season, so please prepare for that. I find myself fantasizing of some future day when new pediatric trainees won't see hordes of infants hospitalized with RSV bronchiolitis, with worried parents at the bedside.

Second, although I mentioned I didn't see any new data/discussion about strain selection, the covid vaccine discussion had useful updates about epidemiology and risk factors, mainly from the Haver presentation on June 27.

About half of children hospitalized for covid had no underlying risk factors; we already knew that, but here's a more detailed breakdown. Note that these numbers are for the past year, at time when virtually all US children had some prior antibody from infection and/or vaccine.

Here is the vaccination status, including the low numbers who received the 2023-24 version, of the hospitalized children:

One BIG disappointment for me with the presentations: there was no mention of a control group - i.e. what are the rates of underlying medical conditions and 2023-24 vaccine status in the pediatric population as a whole? Adjusting for rates in the general population would provide a better estimate of the relative contributions of risk factors and vaccination to more serious outcomes and give us a better handle on the magnitude of benefit of vaccination, for example. Still, nothing has changed; for the individual child, covid vaccination is better than not being vaccinated, even factoring in the low rates of serious outcomes and adverse vaccine events in children.

The 2023-24 vaccine was highly effective against emergency department and urgent care visits in all age groups, though waning of protection over time was seen. Lack of enough events of hospitalized children precluded reliable estimates of VE against pediatric hospitalizations. (Link-Gelles presentation June 27.)

Bird Flu

Exciting (to me) news that CDC is collaborating with the Michigan health officials to carry out a seroprevalence study for H5N1 infection in Michigan dairy workers. This should produce much better information about asymptomatic and mild infection in humans and possibly lead to more clues about transmission.

Covid Uptick?

Still a question, but positive test percentages are increasing, albeit at a low level and predominantly driven by western states.

Wastewater variant detection is lacking across the country, see all the block dots (no sequencing data) below, but you can magnify your area of the country and find a few sites with enough data to determine predominant covid strain.

For example, in my neck of the woods most of the sites have no sequencing data. Of the 2 that did, one showed a predominance of KP.2 and the other LB.1. Nationally, KP.3 is starting to exceed KP.2. Again, we're still at low numbers.

A Tip of the Hat to "The Simpsons."

I knew that "meh" might have been adopted from a Yiddish term meaning so-so or unimpressive, but it looks like a 1994 episode of the TV series The Simpsons, featuring ultraconservative Sideshow Bob, popularized the term. Lisa Simpson was investigating voter fraud as the reason Sideshow Bob was elected as Springfield's mayor, and the "meh" word was uttered by a Hall of Records bureaucrat when Lisa expressed disbelief that he would give her the entire mayoral voting records that should have been kept secret. (Thie episode is available only with subscription, but I verified the quote at about 15:30 time in the recording.)

Voter fraud 30 years ago?

Published on Leave a comment on Are You an Owl or a Lark?

Another round of Daylight Saving Time. I came across a new article suggesting that potential harms of DST depend on your individual chronotype, or, more simply, whether you are an owl or a lark. I definitely fall into the lark category. More on this later, but let's dive into what's been happening in pediatric infectious diseases the past week.

New IDSA Laboratory Test Guidelines

Just out is an updated guideline from the Infectious Diseases Society of America. It might be my favorite guideline of all time, but at 244 pages I recognize it's not for everyone. Let me mention a couple items that I notice some frontline healthcare providers may not know about but are important to avoid misleading test results (a garbage-in-garbage-out scenario).

First concerns the use of swabs, starting on page 8 of the pdf guideline document. Always use a swab for sampling throats, conjunctiva, superficial wounds (aerobic culture only), some nose, nasopharynx, and vaginal testing, and sometimes in special circumstances related to institutional- or manufacturer-related instructions for the product. Never use a swab for surgical tissue - submit the tissue itself making sure it doesn't dry out before processing. The same applies for "respiratory fluids and secretions, endophthalmitis and keratitis, nasal sinus, otitis media, biopsy, abscess fluid, fungal and acid-fast bacilli specimens, formed stool, epiglottitis, diarrheal illness, and when anaerobes are suspected opt for tissue or fluid in anaerobic transport... Never submit a swab for analysis that has been dipped into a fluid or exudate. Send an adequate volume of the fluid or exudate instead." There's also an in-between situation where larger volume sampling isn't feasible, such as with an open wound (at least obtain a needle aspirate of leading edge).

The second pertains to urine specimens, the bane of my existence when consulting on possible UTI based on specimens that have sat around for considerable time before processing, such as placed in a lab collection box in an outpatient setting. Some key points, starting on page 119: "Urine collected for culture should not be kept at room temperature for more than 30 minutes. Hold at refrigerator temperatures or utilize a preservative tube if not processed by the laboratory within 30 minutes." The authors also mention the perils of relying on urinalysis because techniques have not been standardized and often require subjective interpretation. Especially if you are dealing with a child with possible UTI, obtain a good mid-stream voided or catheterized urine specimen and, again, don't let it sit at room temperature too long before analysis.

Different considerations arise when sampling urine for sexually transmitted infection - here, the first portion of urine voided is best for detecting pathogens by nucleic antigen amplification testing.

Speaking of Throat Swabs

The biggest problem in diagnosis of streptococcal pharyngitis is performing throat testing in children highly unlikely to have streptococcal pharyngitis. In this setting, a positive result is much more likely to represent a clinically-irrelevant carrier state and result in unnecessary antibiotic exposure for the child. Some heavy hitters in the group A streptococcal world published a review on this recently, but unfortunately it is not available without subscription to the journal. The authors describe differences in GAS testing between the US and Europe, compare and contrast rapid antigen detection and NAAT testing, and again mention situations where testing should not be performed: children less than 3 years of age unless known exposure, children with signs of viral infection including cough, runny nose, or hoarseness, and absence of "bona fide" clinical suspicion for strep throat if you use a clinical scoring system such as Centor or McIsaac.

Nirsevimab Worked Liked We Hoped

Nirsevimab effectiveness was 90% in preventing hospitalization for RSV infection in infants during their first RSV season, according to CDC data on 699 hospitalized infants. This is actually at the upper end of the confidence interval from prior clinical trials.

AI for Otitis Media

I seem to be on a track of personal banes of my existence as a consultant; misdiagnosis of acute OM is near the top. Although I don't see any of us being replaced by artificial intelligence anytime soon, a new report has some glimmer of hope that it might help us with AOM. It uses a not-yet-available iPhone app with an otoscope; you can use voice to control when to take a photo. Watch the video (at the link to the article, not in the screenshot below) to get an idea of what's involved. It's not nearly ready for prime time, but stay tuned.

Is Covid a Risk for Development of Autoimmune Rheumatologic Inflammatory Disorders?

This study of millions of adult patients from Korea and Japan utilizing a claims database would suggest that it is, with adjusted hazard ratios around 1.25 - 1.3. So far this is just an association and does not determine causality. Also, genetic risks for autoimmune disorders differ in Asian versus US populations (think Kawasaki Disease), so the results may not be broadly applicable.

Influenza is Still With Us

I've officially retired my WRIS (Winter Respiratory Infection Season) section. Really we're only waiting for flu to wind down, though we still have too many covid hospitalizations and deaths. Here's the most recent Fluview map, looking a little more encouraging:

In the meantime, the FDA VRBPAC met on March 5 to officially recommend trivalent vaccines for next fall. The disappearance of the B/Yamagata lineage means we won't need a quadrivalent vaccine as in past years. Next up is CDC/ACIP recommendation in June.

Medical Injustices in the Past

It was painful for me to read, but I highly recommend the NEJM series highlighting medical injustices and biases perpetuated in its publications. The current article is about eugenics. Apparently there were a few voices trying to speak up against these practices in the early part of the 20th century, but they were drowned out by the majority, many of them physicians. You don't need a subscription to the journal for this series.

My Inner Lark

On a lighter note, I was delighted to learn that I might not be at such high risk for adverse events of Daylight Saving Time. A recent study looked at the effects of the DST change on sleep and work productivity in 155 full-time workers in Germany utilizing survey methodology. The effects varied with individual chronotype; that is, the "owls" are those that tend to stay up and wake up later than "larks," the early to bed and early to rise group. There's actually a tool to determine chronotype! The study found that us larks are less affected by the shift to DST.

Lots of evidence exists that the DST shift is associated with harmful effects, from medical illness to car crashes to work productivity. However, this is an extremely messy phenomenon. We have good evidence that the shifts are associated with poor circadian rhythms, a biologic plausibility for harmful outcomes, but only an epidemiologic association with these bad outcomes. With too many factors that can't be controlled or accounted for, probably the only way we will know if DST is bad is if the bad outcomes lessen when we quit using DST. I recall 2 prior instances where an epidemiologic association was likely confirmed to be causal: the association of aspirin use with Reye Syndrome in children, and the association of infant sleeping position with Sudden Infant Death Syndrome. The aspirin industry fought against the concept, but Reye Syndrome essentially disappeared when aspirin use for symptom relief in young children ended. SIDS rates plummeted with the Back-to-Sleep programs.

I don't recall ever seeing a lark, but apparently a subspecies of horned lark inhabits Maryland. I guess I'll need to rise early to spy one.

From CornellLab All About Birds.

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