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Last week's post dove into the dog days of summer, and another article this week kept my canine focus centered; I learned about a new breed to me, the Pyrenean Mountain Dog.

New Hope for Group B Strep Vaccine?

I don't usually hype phase I or phase II trials, but this past week's article in the New England Journal offers a glimmer of hope for maternal GBS vaccination to prevent neonatal disease. Maybe it's just wishful thinking, but we might have a breakthrough after decades of failures. We'll need to wait for a definitive phase III trial before we know. I refer you to the accompanying editorial by Carol Baker, the investigator most responsible for "discovering" the emergence of neonatal GBS disease in the 1970s. As in aside, I was a subject in her phase I trial of a GBS vaccine in the early 1980s. The fact that she was my fellowship director at the time wouldn't pass ethical muster today, but I had no side effects and I recall that I did have a good antibody response. Still, that vaccine didn't make it past further testing.

Bacterial Vaginosis

Other than neonatologists, most pediatric providers don't think about BV that often. However, it is very likely a factor contributing to preterm delivery. It's a confusing infection, or perhaps better termed a dysbiosis, consisting of vaginal colonization with various anaerobic bacteria and absence of lactobacilli. A few diagnostic criteria have been in use, but lately molecular screening tools have improved. A new study suggests that molecular screening of pregnant people could be cost effective in preventing pre-term births by identifying individuals with BV and treating them early. Investigators randomized 6671 pregnant people before 20 weeks gestation to have self-administered screening swabs versus regular care. Molecular testing was with a research (not commercially available) tool looking for high levels of Atopobium vaginae and/or Gardnerella vaginalis, and those testing positive were treated with azithromycin or amoxicillin. The differences in the rates of pre-term births in the treatment (3.8%) versus control (4.6%) groups were not statistically significant. However, results in the 3000+ nulliparous (could have had previous miscarriage or abortion) subjects did reach significant difference: 3.6% versus 5.9%. In my current telemedicine practice I see many pregnant individuals who have undergone some type of BV screening. I'm hoping more studies like this will shed light on this somewhat confusing dysbiosis.

More Tick Reminders

Folks at the CDC remind us about tickborne relapsing fever, aka soft tick relapsing fever (STRF). As the name implies it is a relapsing/remitting type of fever and can be pretty tough to diagnose, especially since it isn't seen equally in all parts of the US and is reportable only in 12 states (Arizona, California, Colorado, Idaho, Montana, Nevada, New Mexico, Oregon, Texas, Utah, Washington, and Wyoming) as of 2021. Think of it in campers or others who are active in the outdoors who have had recurrent fevers. CDC investigators reported on 251 cases over a 10-year period, 61 < 18 years of age. Here are some key geographic and clinical points to keep in mind for diagnosis:

'Demic Doldrums

Things remain calm, with a few things to report. Pediatrics published a supplement on covid and school management a couple weeks ago, took me a little while to go through everything. Hindsight usually is 20/20, but I'd say with the pandemic it's more like 20/60, largely due to incomplete data and a moving target with viral variants. However, I would draw your attention to one of the article about lessons learned. The authors include 8 lessons learned; I would put most of this still in the realm of opinion but it is well-reasoned:

  • School closures were necessary initially but should have been shorter
  • Masking works in schools (covered in 2 of the lessons)
  • In-person teaching with masking is better than school closure or hybrid education
  • Covid exposure is not a good reason to exclude school attendance
  • Efficacy of school ventilation improvement is not well-substantiated
  • Asymptomatic screening is ineffective
  • Vaccine trials should be carried out in adults and children in parallel, rather than delaying pediatric trials until adult data are available

Also in both covid and canine realms, the Pyrenean mountain dogs pictured below are actually sniffing out covid.

A new article reviewed evidence to date of dogs trained to sniff out the infection through various methods. A variety of dogs were trained, including mutts. However, the numbers are very low; it's hard for me to imagine a practical use of covid-sniffing dogs, but maybe this will lead to an effective breath test.

You also may have heard nirsevimab, the long-acting monoclonal antibody to prevent RSV in young children, was officially approved by the FDA. Next up is a CDC/ACIP meeting on August 3 to discuss nirsevimab and maternal RSV vaccination, with votes scheduled on recommendations for use.

Playing Games

No, I didn't forget that challenge in last week's post. Blame one of my sons for this. He told me that the New York Times games and puzzles are major revenue sources for the publisher. I receive bupkis for this blog, but I'm not above trying something that might keep readers interested. I couldn't find a credible study for his claim, but there is some evidence.

So, the answer to last week's challenge of the correct number of weather- and temperature-related references and puns in the Dog Days post is 16, including 1 in the Title (summer), 1 in the intro (steaming), 4 in the Bugs section (heating up, hot off the presses, febrile illness, tip of the iceberg), 2 in hep C (cool, clouded), 4 in 'Demic (hot air, cooled, boiling point, hot spots), and 4 in the Astrology section (summer, heat, cool, thunderbolt). Decision of the judges (me) is final.

And by the way, my house is back in the cool as of Friday, unfortunately following purchase and installation of a new air conditioner.

The covid state of emergency has ended, both globally and in the US (the latter officially on May 11). On May 4, the director general of the World Health Organization, Dr. Tedros Adhanom Ghebreyesus, declared that covid is now an established and ongoing health issue that no longer requires resources needed for a public health emergency of international concern (known in the business as PHEIC). Future planning from the WHO is now detailed in a new document, the 2023-2025 COVID-19 Strategic Preparedness and Response Plan. It weighs in at only 20 pages, so needless to say it is short on details. For that, you'll need to dig into the document links.

Meanwhile in the US, our official emergency will end on May 11 as previously planned. So far we don't have any true future response plan.

Funding for Vaccines, Medications, and Tests

The official end of the emergency eventually means that the general public won't have access to free covid vaccines, medications and diagnostic tests. Naturally this varies with insurance type and also timing; any products still in circulation that were provided by the feds will remain free, but I haven't seen any estimates yet on how long these supplies will last. Nothing will really change for patients on Medicaid until September 2024, although access to Medicaid itself could change. The Infectious Diseases Society of America (IDSA) produced a nice table briefly outlining the situation. Unfortunately it's too big to copy well below, but a pdf version is available for download. Note that this all is completely separate from FDA's Emergency Use Authorization for vaccines, medications, and devices, which won't change until industry applications for full approval are submitted and evaluated.

Covid Vaccine Updates

First, I very much apologize for not mentioning in last week's post that the FDA on April 28 did make some allowances for additional vaccine doses for immunocompromised children. CDC has now posted this update in their Interim Clinical Considerations website for covid vaccination. Basically, any significantly immunocompromised person 6 months of age and older can receive additional bivalent vaccine, number of doses depending on prior vaccination status but also giving much leeway to the healthcare provider. Sadly, the site is still very messy, not user friendly for providers or individuals. CDC and IDSA did have a webinar on May 4 with some nicer graphics in some slides, but so far I've been unable to find the same graphics on the CDC website. Here's the quick look at vaccination for immunocompetent children ages 6 months to 4 years, and also for that "awkward" age of 5 years when the cutoffs for Pfizer and Moderna vaccines are different. You can download or watch the presentation yourself at the IDSA site.

The next major step for covid vaccines will be a meeting of the FDA's Vaccines and Related Biological Products Advisory Council (VRBPAC) on June 15. At that time the composition for the next vaccine will be determined, in time for a potential release in fall of 2023. The FDA's plan for subsequent covid vaccine adjustments was presented by Dr. Peter Marks, director of FDA's Center for Biologics Evaluation and Research, at the same May 4 IDSA meeting mentioned above. It is very similar to the process for annual influenza vaccine composition.

Covid Tracking Changes

We've been in more of a bind the past several months trying to track covid cases in an era of public exhaustion with the pandemic as well as non-reporting of home testing results. Additionally, CDC and local/state health departments have lessened their efforts, and most non-governmental groups have discontinued intense tracking as well. We are mostly left with tracking easily measurable data that probably are a good surrogate, at least for severe infections. Hospitalization rates for covid have been quite low for all age groups recently.

On May 5 CDC released 2 MMWR articles to clarify and justify tracking changes. Primary surveillance now will consist of the weekly hospitalization rates above as well as percentage of deaths attributed to covid. Secondary indicators are emergency department visits and percentage of positive covid testing in laboratories. Genomic and wastewater surveillance will be used to track variants. In the past, many of these outcomes have reflected in a timely manner the covid community levels when tracking of infection was more reliable, so perhaps it's not a bad trade off. Time will tell.

Other Changes and Events

The news has been saturated with Dr. Rochelle Walensky's announcement that she will step down as CDC director effective June 30. The announcement was short on rationale for the change. Previously Dr. Walensky had announced new strategic planning to revise CDC's structure and management, a badly needed overhaul. I hope this plan won't fall apart with her departure.

As I mentioned in a February posting, work on RSV vaccines is advancing, most recently with FDA approval of one vaccine for individuals 60 years of age and over. CDC and ACIP are expected to make recommendations at their June 21-23 meeting. Flu vaccine composition also will be discussed. In the meantime, FDA VRBPAC will discuss RSV vaccination of pregnant women to prevent or modify illness in newborns at their May 18 meeting.

Lastly, you may have seen press reports of a meeting of scientific advisors with the White House that attempted to put a number on the likelihood that we'll experience another big wave of covid in the next 2 years. Like all covid forecasts, many assumptions are made to produce such numbers and really should be accompanied by a sensitivity analysis that varies the assumptions so that we have a better range of what to expect. I haven't seen an actual publication for this latest estimate so can't really comment further.

My Book Report

I've been working on a book review that I hope to have completed in time for next week's blog. I'm also trying to remember when the last time was that I wrote a book report, probably elementary school. Stay tuned.

I knew my week would be busy with some holiday event planning, but it got busier with a lot of infectious diseases happenings to keep track of. Let's dive in.

RSV

CDC provided a summary of RSV seasonality over the past few years. It's a nice look at how the pandemic affected circulation of this common respiratory virus and perhaps gives us a glimpse of the future. The graph below depicts the seasons based on percent PCR sampling positivity.

The 2019-2020 season was a typical one, peaking well before covid pandemic practices kicked in. Look at the 2020-21 season, with the winter RSV season completely gone but then a very atypical rise starting in May/June and contributing to an early but blunted summer and fall season for 2021-22. The solid black line for 2022-23 looks like a more typical season with a bit of an early peak as masking and social distancing disappeared. Next year should continue with a more standard RSV season unless we have some dire new covid variant that results in a return to masking and other nonpharmaceutical measures to reduce illness.

I was initially hopeful that the online publication of the Pfizer RSV vaccine trial for pregnant women would include results from the most recent RSV season, but alas it did not. I mentioned this topic in my February 26 posting, and now those data appear in a peer-reviewed publication. The trial enrollment was stopped last September because efficacy was demonstrated for one of the primary outcomes, but women and their newborns already enrolled will continue to be followed. I hope data from this past RSV-intense season will be analyzed and released soon.

Severe Group A Streptococcal Disease

Last week saw 2 new studies published, with slightly different focus and different findings. A group from the Netherlands focused on GAS meningitis, studying CSF isolates from 1982 to mid-March 2023. The study included all ages. They found that a particular subtype, M1UK was more dominant during the recent uptick in severe GAS infections.

A group in Houston looked just at a pediatric population for all invasive GAS disease, finding a different subtype over-represented recently (emm12 versus emm1 previously). The saga continues.

Marburg Virus

Haven't heard of it? It's another in the hemorrhagic fever group of viruses, like Ebola, and it is now bubbling up in parts of Africa (Equatorial Guinea and Tanzania) resulting in a Health Alert from the CDC. A recent timely editorial, written before the Tanzanian cases appeared, provides a little background. Be sure to get a good history from returning international travelers, plus warn any of your patients planning travel to these areas.

Covid

We all know covid isn't going away, and the past couple weeks provided a bit more confusion that we didn't need. First, we saw another publication about SARS-CoV-2 origin, interesting but not at all definitive. A sad report of 2 cases of severe neurologic manifestations in young infants, probably linked to in utero infection, describes in detail various clinical, histologic, and virologic features. It is this type of basic research that will expand our understanding and perhaps lead to more effective interventions.

Last but certainly not least, I want to address an important question posed by Dr. Hilary Deutsch: "What did you think about WHO not recommending Covid vax because there were “only” 17,000 pediatric deaths from Covid worldwide?" The news report commented briefly about this, importantly stating "The low priority group includes healthy children and adolescents aged 6 months to 17 years. Primary and booster doses are safe and effective in children and adolescents. However, considering the low burden of disease, SAGE urges countries considering vaccination of this age group to base their decisions on contextual factors, such as the disease burden, cost effectiveness, and other health or programmatic priorities and opportunity costs."

Digging a little deeper, you can view the agenda for the entire meeting and access various slide presentations by downloading it and opening in Adobe Acrobat. The covid session is entitled "Roadmap for COVID-19 Vaccination in the era of Omicron" and consists of 75 slides; it is a very complete analysis. The bottom line comes down to the quotation from the news release in the previous paragraph. WHO needs to provide global guidance, and situations in different countries are very different of course. So, this is an attempt to help health officials make a judgment that best suits their particular setting. This is not just an issue for countries with severe resource constraints. For example, the United Kingdom recently proposed targeting "clinically vulnerable" 6-month to 4-year-old children for their vaccination program. They do not advise vaccinating healthy children in this age group.

Comparatively speaking, healthy children and adolescents are a low-risk population for serious outcomes from covid. From a public health view, especially if resources are limited, it may be best to direct priorities to higher risk groups. From a personal or family perspective, it is still clear that covid vaccination versus no vaccination is the better choice to avoid serious outcomes, even in low risk individuals. I would still maintain that the "contextual factors" in the US still favor recommending covid vaccination for all, including healthy children starting at 6 months of age.

So Much for Retirement

I thought I had retired from clinical practice several months ago, but now I've been cajoled out of my bliss to help with some new subspecialty ID consultations at regional hospitals in DC, Maryland, and Virginia. So, I've unretired for now with new permanent retirement delayed somewhat. Any resemblance of my situation to Tom Brady's is purely coincidental (obviously).

Lots of pediatric infection-related meetings and reports this week, but actionable items for front-line care providers were sparse. It's not that the information wasn't interesting, but when all was said and done I couldn't come up with anything to change clinical practice. That type of noise is good, but I'll be more excited a few months from now when we might have actionable events from ongoing studies.

A 3-Day CDC Advisory Council on Immunization Practices (ACIP) Meeting

This ACIP meeting covered a lot of vaccine topics including vaccines for mpox, influenza, pneumococcus, meningococcus, polio, RSV (both pediatric/maternal and elderly adults), chikungunya, dengue, varicella, and our old friend covid. I wasn't able to view the sessions live but have reviewed many of the slides that were posted. The only vote at the meeting was to continue use of mpox vaccination pretty much as before; the rest of the meeting primarily consisted of updates. In the next few months we should be approaching some decisions particularly for RSV immunization of pregnant people to protect their newborns, long-acting monoclonal antibody treatment to prevent RSV in high-risk and/or all infants, 20-valent pneumococcal vaccines for children, and more.

With regard to RSV prevention, in the past I was struck by ACIP wording about anti-RSV monoclonal antibody therapy being labelled a "vaccine" when it really is a therapy. I now understand that the vaccine label would have made it easier to provide the intervention through the Vaccines for Children program; if it is a therapy, some infants will fall through the cracks in terms of access. AAP had a nice summary of these issues.

Pfizer presented data that they have submitted to FDA for maternal RSV immunization during pregnancy to prevent RSV in their newborns, but I won't show that data since it was only from the pharmaceutical company without separate analysis by ACIP or CDC. FDA/VRBPAC will discuss RSV vaccines for people 60 years of age and older (this also was discussed at the ACIP meeting) on February 28 and March 1, but it doesn't look like they will cover any pediatric issues at this meeting. However, if studies look good it is possible we will have new interventions to prevent RSV in young infants prior to next winter's RSV season.

Post-Acute Sequelae of COVID-19 (PASC)

I did attend a February 23 webinar on PASC in children and adolescents hoping to see some new data, but ultimately I was disappointed. That's not to say that progress hasn't been made, but the session was mainly a review of previous data and guidelines. I did learn that risk factors for PASC in children and adolescents include age greater than 12 years, unvaccinated status, and history of allergic disease. PASC symptoms were less common in vaccinated individuals than in the unvaccinated. Here's a peek at main symptom frequencies:

It was a good review session of general evaluation and treatment options, check out the complete slide deck.

PASC is really a tough issue, likely because it is still a mixture of at least 2 different processes. One includes all the end-organ damage from the infection itself, while the other comprises more vague manifestations such as brain fog, fatigue, and dysautonomia symptoms. I've been seeing children with these conditions long before the covid era, seemingly following a wide variety of otherwise run of the mill infections. I'm hoping the intense research focused on PASC will yield something useful for the larger body of individuals affected with what has been called myalgic encephalomyelitis/chronic fatigue syndrome. I dislike that term, it still sounds somewhat pejorative to my ears. Of note, the National Academies of Science, Engineering and Medicine is planning a series of workshops to better characterize a working definition for Long COVID.

We Still Have a Failure to Communicate

Just a quick mention of a study that reviewed US state and territory public health sites for readability and accessibility of their covid treatment information. Broadly speaking, most sites fell short of effective communication - wording too technical or at a high reading level, not helpful for individuals with communication barriers, etc. South Dakota was the best site, followed by Maine and Tennessee (would you have guessed these states coming out on top?). You might want to look at where your state scored. I'm hoping public health units see this article and work to improve their sites.

Enough Ivermectin Already?

Well, yet another study has shown no benefit of ivermectin as a covid therapy, this time using a higher dose. I was more enthralled with one of the accompanying editorials about the ethical principle of equipoise in performing clinical trials to deal with uncertainty in medicine. Simply put, it's a good idea to perform clinical trials to deal with uncertainty, but given that we always have uncertainty in medicine, when should we call it quits for these trials? Specifically, when does it become unethical to perform studies of ivermectin for covid in the hopes of finding some small niche where there might be benefit? That question has no easy answer. Ivermectin became a political pawn early in the pandemic; I fear the end result of that conflict is now wasted resources and unnecessary risks for trial subjects.

Better Data on Paxlovid Rebound

We were just talking about this last week, and now we have results of a prospective study that gives us perhaps even better data. Both viral and symptom rebound were slightly higher in the Paxlovid group compared to controls, but pretty much still in the same ballpark. For example, symptom rebound was about 14% in the treatment group and 9% in the controls. The prospective design of the study is more likely than retrospective studies to give "truer" numbers, and I think what we are seeing is that rebound is more common in untreated people than originally thought. From my viewpoint, the slight increase in rebound from Paxlovid is far outweighed by the benefit of treatment in preventing complications in high-risk individuals.

White Noise

Speaking of noise, this past week my wife and I watched Noah Bambach's adaptation of Don DeLillo's novel, White Noise. Buried somewhere in the few hundred books in our house is a copy of the novel, but neither of us could remember plot details. Fifteen minutes into the movie, we realized neither of us had ever read it!

It's an understatement to say that reviews of the movie were mixed; in fact, many were at the extremes of love or hate. This isn't surprising for a book that was said to be impossible to translate to the screen. Yes, the movie had its dragging and confusing moments, but I loved it so much that I decided to read the book. I'm almost done with it, and it's very interesting for me to see what elements Baumbach left out or changed substantially, versus other parts taken nearly verbatim from the book.

The book, written in 1985 and dealing with fears of mortality, a college professor and his family, and an "airborne toxic event," sadly translates very well to today's chaotic world. The movie was mostly true to the book's central themes, and the song and dance ending, a backdrop to the closing credits, made me smile. I'd recommend both the novel and the movie to folks who might enjoy a quirky, reflective view of modern life and be able to put up with some unevenness in presentation.