This past week I attended an event that led me to reflect on "good will," not necessarily referring to the "peace on earth ...." quote or to the San Antonio chapter of Goodwill Industries where my mother volunteered countless hours in the last century, but a more basic understanding. Its origins may be in the New Testament or in Middle English, but regardless it is pertinent today. More on that later.
Maternal RSV Vaccine Approved by FDA
The approval finally came through, as it turned out on the last day of FDA's deadline to make a decision based on the fast tracking and other priorities assigned to it by the FDA. The FDA advisory committee did not meet again prior to this decision, they had already reviewed the data at a previous meeting in May, and FDA did not release any updated scientific documents. Perhaps lost in the fine print is the important change in the approval. The original trials looked at vaccine administration to pregnant people at 24-36 weeks gestation, but the FDA approval narrows this to 32-36 weeks. This significant change is because of concerns about the vaccine causing premature delivery; the numbers in the published trials were very low, not enough to establish a cause/effect relationship and only answerable but post-marketing surveillance when a much larger number of pregnant people receive the vaccine. However, more concern than usual was expressed because another pharmaceutical company (GSK; the approved vaccine is from Pfizer) stopped their clinical trials in pregnant people for the same reason. Delaying the vaccine administration to 32 weeks gestation is a safety move; even if the vaccine causes a higher but extremely low risk of precipitating premature birth, the clinical consequences at 32+ weeks is small; infants born at that gestational age generally do very well. The down side is that narrowing the window for vaccination creates more logistic difficulties in ensuring pregnant people have the opportunity to receive the vaccine.
Next up will be an important meeting of ACIP/CDC to put together all the recommendations, including how to manage use of maternal vaccine and the long-acting monoclonal antibody to RSV, nirsevimab. Their next scheduled meeting is September 12, but so far the only current agenda item relates to covid vaccines.
A Curmudgeonly Jab at the Lay Press
At my age, what else do I have to do besides complain? I was annoyed by 2 items percolating through the lay press this past week.
BA.2.86
This new but relatively rare covid sublineage is popping up in every news feed there is. I've mentioned it before. Although it is present in only very low numbers, the pattern of mutations it carries suggests that it will be very effective at evading immunity from prior infection or vaccines, perhaps including the new XBB-derived vaccine to be available soon. Biobot helps put this in perspective. First, wastewater covid levels seem to have plateaued in the US and are still well below what we say in winter 2023.
Second, this variant doesn't even appear in wastewater data, although note the graph only reflects sequencing through the week of August 7.
In addition to following wastewater data, the next likely useful piece of information should be some in vitro data on ability of serum from study volunteers who received the new covid vaccine to neutralize newer variants, including BA.2.86. Given how long the assays take, we should see some information in September. A silver lining for all the publicity is that it could speed up the peer-review process for publication so we won't need to rely on non-peer-reviewed data. Look for a research letter in the New England Journal of Medicine relatively soon (just my prediction).
You can see the current CDC risk assessment here.
Tripledemic in Kentucky?
My second gripe is with the reporting on a supposed tripledemic resulting in school closures in Lee County, Kentucky, alleged to be caused by a combination of covid, influenza, and group A streptococcal infections. What seems to be missing in all the reports is how these etiologies were established. It sounds like it was just what parents or school staff were calling covid, flu, or strep, rather than based on careful testing.
It's a little early for influenza in Kentucky, not that it's impossible, but so far CDC data haven't shown it.
I didn't find anything about it on the Kentucky state flu site.
Group A strep infections aren't reliably reported, and the problem with GAS diagnoses is the relatively high carrier rate of the organism, around 10-15% in the pediatric population. So, if someone tests a child with a viral illness (e.g. rhinovirus/enterovirus, which is prominent this time of year), 10-15% will test positive for GAS.
More reliable but less relevant to Kentucky are recent data from England about GAS hospitalizations:
This may reflect changes in epidemiology during and after the pandemic, but I'm still skeptical of the characterization of etiologies for the Kentucky school illnesses. I hope we'll hear more eventually.
Fungus Amongus
I received a COCA Now notice from the CDC nicely summarizing concerning trends in fungal strains causing ringworm and nail infections. It may be that we are in the midst of rising rates of resistance to commonly-used antifungal medications to treat these diseases. A big problem for clinicians is that treatment response may be normally slow, requiring weeks to months of therapy, so it can take a long time to figure out if the infection isn't responding. Keep this in mind if you notice children with poor responses to treatment, and consider culture and susceptibility testing with a qualified lab.
Paxlovid Resistance
No surprise to anyone, but a new report characterizes nirmatrelvir (Paxlovid) resistance in an immunocompromised patient, exactly the sort of setting we'd expect to see for development of resistance. This isn't the first report of Paxlovid resistance, and it won't be the last. I wouldn't worry about it yet, but, like most treatments for infectious diseases, resistance becomes a problem sooner or later.
My Night in a Brewpub
Not one of my usual habitats, but this was for a good cause: a special meeting of the Greater Washington Infectious Diseases Society at a brewpub in Bethesda, MD. You won't find a web link for GWIDS, not because it's a secret society but because no one has gotten around to making one in the few decades of GWIDS' existence. It's a monthly meeting of adult and pediatric infectious diseases training programs in the DC area where fellows in training present challenging and usually obscure infection cases and try to stump the stars in attendance. Basically it is heaven for an infectious diseases nerd.
This meeting was our first in person since the pandemic began. It was special because Dr. Anthony Fauci, an annual speaker usually at the end of the year, was featured in what was supposed to be a fireside chat now transformed into a vatside chat. I moderated the session only because the first 50 or so choices for moderator weren't available. We gathered a list of questions from members prior to the meeting plus opened up for questions from the audience at the end. A good time was had by all, although I myself missed out on the refreshments.
One of the questions I asked, the only one I submitted, was for Dr. Fauci to help us understand the differences between the criticisms he received during the early days of the AIDS pandemic and the terrible threats he now receives from various covid crazies. (Three guys looking very muscular, with receivers in their ears and bulges under their coats, were the only non-GWIDS members present; Fauci came and went in one of those flashing-light black SUVs that disrupt traffic all over the DC area.)
In 1988, Larry Kramer, one of the earliest AIDS activists and a leader in the movement (also an accomplished playwright and author), published letters to Fauci in the Village Voice and the San Francisco Examiner. I read excerpts from those documents, and if you didn't know the context it would be perfectly reasonable to assume they were written recently. Kramer called him a murderer, an idiot, and a liar, among the repeatable epithets. I can't quote Dr. Fauci's response accurately, I wasn't taking notes, but the gist of his reply was that the AIDS and covid personal attacks, while sounding similar, are completely different. The difference boils down to Good Will.
AIDS protesters wanted to work to a solution; they were terribly critical of Fauci as a person as well as of policies of FDA and NIH. The end result was a revamping of the research and approval process for AIDS (and thus other treatments) that resulted in a quicker and more effective benefit to society. According to Fauci, those AIDS activists were motivated by good will and demonstrated willingness to collaborate on a solution. Nothing like that exists in today's Fauci demonization.
Read Tony's NY Times essay on Mr. Kramer and "loving difficult people," and take a little time to practice some good will.
