I hope everyone had a wonderful Thanksgiving holiday, I know I did. With 4 physicians and 2 other medical professionals at the the table this year, our family went through the usual dressing/stuffing discussions with risk of undercooking the stuffing resulting in higher salmonellosis risk. We remain asymptomatic.
Recently I watched a 3-part PBS series about the artist Frido Kahlo. It also featured her sometimes-husband, Diego Rivera, prominently; he was a better known artist than Kahlo for much of the 20th century. Little did I know, until a hot-off-the-presses review article, that he had a bit of microbiologic art featured in some of his works.
First, let's look at what's been going on, besides Thanksgiving, this past week.
Strep Throat Should Be Simple
Every now and then I go on a rant about strep throat. Of course sore throat is very common, and it sounds like a simple problem, but in fact it is one of the most poorly understood maladies I deal with. The combination of a common clinical problem with a pathophysiologic basis full of lacunae has resulted in generally poor management, most conspicuously in antibiotic overuse. The biggest problem is trying to determine someone who tests positive for GAS is just a streptococcal carrier who really has viral pharyngitis from someone with true streptococcal pharyngitis who would benefit from antibiotic treatment. With rare exceptions, identifying a streptococcal carrier is of no clinical utility and only serves to increase unnecessary antibiotic use. We badly need better diagnostic tools (both clinical and laboratory) as well as a better understanding of drivers of serious sequelae such as invasive disease and post-streptococcal arthritis, rheumatic fever, and glomerulonephritis.
Now we have a very intriguing study of essentially healthy children presenting with sore throat and then followed as a prospective cohort for 2 years, looking specifically at antigen testing, throat culture, streptococcal antibody levels, and outcomes. It was mainly designed to provide a framework with which to test upcoming vaccines for group A streptococcus - if you don't have accurate inclusion criteria and outcomes, it's pretty tough to measure vaccine effectiveness. I want to also mention here that of the 8 authors, only 1 was an actual clinician; the rest were all employees of a pharmaceutical company that develops vaccines. Normally that degree of for-profit pharma involvement in a trial would raise concern for implicitly biased interpretations of the results, but in this case we don't have a vaccine product involved in the study so perhaps less for me to fret about.
Children could be enrolled if they were from 3 to 12 years of age and did not have circumstances that could alter conclusions, including no documented group A streptococcal infections in the 6 months preceding study entry. Here's the protocol at study entry at the time of presentation with sore throat (RADT denotes a rapid antigen test for GAS):
![](https://blogs.gwu.edu/bwiederm/files/2023/11/Screenshot-2023-11-25-at-3.37.36 PM.png)
Study subjects then had healthy visits at 3-month intervals for the remainder of the 2 years, as long as it was at least 6 weeks following sick visits. At the healthy visits they had throat culture for GAS, but not RADT, obtained. Serology for the sick visits included blood for antistreptolysin O, anti-DNase B, and antistreptococcal C5a peptidase antibodies. If GAS pharyngitis was diagnosed at sick visit 1, the children were treated as per standard by their clinician.
Definitions are important here. A GAS carrier was defined as a positive healthy visit GAS culture plus a positive RADT or culture at sick visit 1 that remained positive at sick visit 2 which occurred 7-10 days after completion of antibiotic therapy for the sore throat event. The researchers evaluated several definitions for GAS pharyngitis which I copy here:
![](https://blogs.gwu.edu/bwiederm/files/2023/11/Screenshot-2023-11-25-at-3.50.01 PM.png)
I provide a lot of background for the study methods because they seem very well considered to me, plus I think it is helpful for clinicians to consider all of these possible case definitions when evaluating children with pharyngitis.
Now for the results. First, streptococcal antibody measurement is mostly useless to distinguish true infection from carrier state. That could have been predicted from multiple prior studies but is particularly important in monitoring antibody response in vaccine trials.
Don't look to this study to change your clinical practice if you already follow guidelines for management of GAS pharyngitis. What it does show is how difficult it will be to design trials for future GAS vaccine effectiveness. In the 1960s, a GAS vaccine likely caused an increase of acute rheumatic fever-like illness in vaccine recipients, and GAS vaccine development has been appropriately cautious since that time. GAS vaccine safety issues have been reviewed recently.
Also be aware that I had a few questions about the study that weren't addressed in the publication or the accompanying online supplemental information. I've emailed the first author, the one clinician in the study, and if I hear back I'll provide updates.
It's Beginning to Look a Lot Like ...
.... winter respiratory virus season. RSV, influenza (sorry, at the time I'm writing this we have no new FLUVIEW updates since the week ending November 11), and to a lesser extent wastewater covid all are on the upswing,
![](https://blogs.gwu.edu/bwiederm/files/2023/11/Screenshot-2023-11-25-at-2.45.28 PM-1024x812.png)
![](https://blogs.gwu.edu/bwiederm/files/2023/11/Screenshot-2023-11-25-at-2.51.07 PM-2-1024x451.png)
It doesn't qualify as a tripledemic yet, but stay tuned.
The Verdict on Last Season's Flu Vaccine
The 2022-23 influenza season was a bad one for pediatric hospitalizations, but we now have some final data on how well the influenza vaccine prevented such episodes.
![](https://blogs.gwu.edu/bwiederm/files/2023/11/Screenshot-2023-11-25-at-3.02.49 PM-1024x507.png)
The vaccine effectiveness is pretty good, in line with other seasons for the most part. The low vaccination rates are another key takeaway; I wish this would improve, but I'm not optimistic given the current upswing in vaccine hesitancy.
Holiday Season Puzzler
Here's a glimpse of Figure 2 from the Rivera review article. As you emerge from what I hope was a wonderful Thanksgiving holiday, see if you can identify the types of organisms that are depicted.
![](https://blogs.gwu.edu/bwiederm/files/2023/11/Screenshot-2023-11-25-at-2.24.15 PM.png)
I have been impressed by the demand , for the largely non available RSV MAB - especially when compared to the almost non existent demand for COVID vaccination in a slightly older age group .
My conclusion is that the issue with influenza vaccine uptake is not primarily vaccine hesitancy - but a sense that the vaccine isn’t effective enough ( same with the COVID vaccine , though parents fear influenza more than COVID for their child )
Those who refuse the vaccine are clearly over estimating the almost non existent risk of the vaccine - but I am ABSOLUTELY - convinced that if we had a vaccine with say 90 percent efficacy for prevention of disease ( not prevention of hospitalization ) that there would be a very high acceptance rate
Hello Dr. Schwartz,
You bring up very important issues about what is driving poor uptake with vaccines nowadays. My general gestalt is that we have a lot of research teams looking into this, but so far I haven't seen a unifying theme nor a true "best practices" for how healthcare providers should approach this issue.
Monitoring RSV preventive measures is an even bigger problem, due to lack of data. We don't yet have any numbers from CDC an percentages or absolute numbers of eligible infants who have received nirsevimab or whose mothers received RSV vaccine at the appropriate time during pregnancy. It's tougher to monitor compared to covid vaccine which was tracked very closely by federal mechanisms. RSV preventive products have been distributed by a variety of mechanisms with less federal oversight, and I think it's going to take a bit longer to get accurate data.
Currently we are essentially dealing with demand outstripping supply for nirsevimab, but so far the absolute numbers of doses available is very small. I wonder if the percentage of eligible children seeking nirsevimab could be as low as the percentage of children seeking influenza vaccine, but the problem is magnified by inadequate supply of the former. We should see accurate data eventually, and regardless of the numbers I hope we gain a better understanding of what drives parental choices for protection for different vaccines.
We should all keep in mind that all 3 of the "tripledemic" respiratory viruses, influenza, RSV, and SARS-CoV2, have effective active and/or passive immunization options.