I'm adding a new post because I heard back very quickly from Dr. Robert Frenck, the first author of the study I mentioned in the last post. He helped me understand the study a bit better.
The study started about 10 years ago and basically represents a pre-pandemic view of group A streptococcal (GAS) epidemiology. It was carried out in outpatient clinics rather than emergency departments or urgent care centers. I was mistaken in how I described enrollment; the children actually entered the study during a well visit and then had subsequent well and sick visit monitoring. I had thought the sick visit was the trigger for enrollment.
The above features make the results more applicable to primary care practitioners, though it's hard to predict whether GAS epidemiology will look different in the post-pandemic era.
Dr. Frenck mentioned some key takeaways from his report: "The biggest thing we were able to re-show is the very high prevalence of GAS in the pharynx of children. I think it shows that many diagnoses of “strep throat” really are detecting colonization. Unfortunately, we did not find a good lab marker to reliably diagnose strep throat."
We're going to hear more about GAS vaccines in the next few years. I'm pretty sure vaccine manufacturers are deep into meetings with FDA staff to devise the best approach for an effectiveness study.
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):
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:
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,
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.
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.
I didn't have any trouble thinking of things to be thankful for this Thanksgiving-time. That might seem odd given the horrific events on the world stage now, and I don't mean to minimize that, but gratitude can coexist with dismay.
First, let's get caught up on this week's ID happenings.
Disappointing Measles News
Measles is probably the most easily transmissible human infection known; a high level (probably 95%) of population immunity is needed to prevent outbreaks. Not surprisingly, a breakdown in immunization rates during the COVID-19 pandemic likely is to blame for increases in measles cases worldwide, as reported last week by the CDC. Concomitant with a decrease in measles-containing vaccine coverage from 86 to 81%, measles cases increased 18% (7.8 million to 9.2 million) worldwide from 2021 to 2022; deaths increased from 96,000 to 136,200. Still, and here's the thankful part, vaccination likely prevented 57 million measles deaths from 2000 to 2022. Here's hoping we can get our global immunization campaigns back on track.
2024 CDC Recommended Immunization Schedules Are Available
Even earlier than advertised, CDC has posted the 2024 immunization schedules. Primary care providers should study these closely due to some complex changes, particularly for pneumococcal and meningococcal vaccines. The AAP has posted a summary of key changes (click on the PDF link). As an aside, I'm a bit irked by what CDC and others call "shared clinical decision-making." Here's CDC's tool for SCDM for meningococcal group B vaccine:
I'm not a primary care provider, but I don't see a lot of help for busy frontline practitioners here. What we really need are more details about choices parents and patients need to consider. Specifically, what are the risks of not getting the vaccine versus those being vaccinated? As stated in the table, meningococcal B infections are relatively rare in the US, so vaccination isn't going to prevent much disease or mortality even with a highly fatal infection. The risks are different depending on individual circumstances. Are frontline providers supposed to have these numbers at their fingertips? Maybe the CDC or AAP will provide them. (Or, if not, maybe I will!)
MIS-C Cardiac Follow-Up
Multisystem inflammatory syndrome in children (MIS-C) following covid infection is very uncommon currently, but we shouldn't forget about monitoring children as they recover from MIS-C. A group at Children's Hospital of Los Angeles reported that even children who did not have clinical cardiac involvement during their acute illness still had some evidence of cardiac injury at the 6-month followup period. Most of the report deals with laboratory, imaging, and other testing, but of the 69 patients evaluated at 8 weeks 15 had clinical symptoms such as chest pain, palpitations, exertional dyspnea, or fatigue. The rate of clinical symptoms was actually lower in the group with no initial myocardial injury, although the difference was not statistically significant. The bottom line: make sure all MIS-C patients have good cardiology followup.
Variations in Influenza Antiviral Use
A group from Vanderbilt reported wide variation in prescribing practice for influenza antivirals during the period 2010-2019 (so, not affected by the pandemic). It is an administrative database study, a study design type that has inherent inaccuracies due to how administrative data is collected. In general, however, a wide variation in practice is an indication that something isn't right. Guideline-concordant compliance was low, for example <40% in children less than 2 years of age, a high risk group. I would have liked to have seen how flu vaccine status affected antiviral use since vaccination greatly lowers risk for severe adverse outcomes, but apparently the database did not contain that information. This is another opportunity for shared clinical decision making with parents; what are the specific rates for infection, hospitalization, etc versus medication side effects (primarily vomiting with oseltamivir) for an individual child, based on their risk factors? That's what a frontline health provider needs when discussing whether to treat a child for influenza.
The "New Normal"
I mention this catchphrase only to bury it. Not only does it seem nonsensical to me, it also is beyond retirement age. Some might wish to apply this catchphrase to the upcoming winter season. I'm strangely thankful/hopeful for this because it now appears we may get to see what a typical respiratory virus season looks like in the post-pandemic era. We haven't seen any weird covid upticks early on, and RSV looks more typical so far without the very severe season we saw last year. Flu may be starting to increase, similar to pre-pandemic seasons. Of course, all of the respiratory virus seasons vary somewhat from year to year. Will covid settle into just another winter respiratory virus?
FLUVIEW is back in business, and the map is heating up especially in the South.
Remember that this is a map of "influenza-like illness" so can capture other respiratory viruses. However, covid wastewater tracking hasn't had much of an uptick.
RSV-NET continues to show increase primarily in younger children, not matching last year's peak but possibly similar to prepandemic waves.
Happy Thanksgiving
I was looking around for something uplifting and fun to mention and happened on "Thanksgiving" by Edgar Albert Guest. Here's an excerpt:
"Greetings fly fast as we crowd through the door
And under the old roof we gather once more
Just as we did when the youngsters were small;
Mother’s a little bit grayer, that’s all.
Father’s a little bit older, but still
Ready to romp an’ to laugh with a will.
Here we are back at the table again
Tellin’ our stories as women an’ men."
I had never read anything by Guest, but I was sold on him when I read his Wikipedia page. Anyone who merits mention by Edith Bunker from "All in the Family," Lemony Snicket, Mad Magazine, and Benny Hill is my kind of guy. Furthermore, Dorothy Parker of Algonquin Round Table fame had the best line: "I'd rather flunk my Wassermann test than read a poem by Edgar Guest." I think maybe she wasn't a fan, but at least she knows her 1950s syphilis testing.
I was thumbing through my Farmer's Almanac this morning and noticed a mention of "Indian summer" for November 12. That's not a great term to use nowadays, so I'm opting for the European version called St. Martin's summer or day. I never bothered to see what these terms really meant, but I've learned it represents a period officially from November 11 to November 20 where we experience unseasonably warm weather. We've certainly had that recently, though November 11 and 12 in Maryland is back to cool fall weather.
Miscellaneous Vaccine News
I have no idea what a "miscellaneous" vaccine is, I was just desperate for something to title this section.
A new vaccine to prevent chikungunya virus infection was approved by the FDA this week for individuals 18 years and older at increased risk for infection with this mosquito-borne pathogen. It is a live virus vaccine. As with most arboviral illnesses these days, the vector range is expanding as our climate warms, and transmission has occurred within the US. Still, most infections in US residents are acquired via travel to more endemic areas such as Africa, southeast Asia, and Central and South America. The clinical illness is similar to dengue fever and mostly is a miserable but self-limited illness. However, elderly are at risk for complications, principally chronic joint disease. Newborns also are at risk for more severe disease, including death, and it is unknown whether the vaccine virus could be transmitted to the fetus. The package insert includes precautions for use in pregnant people. The main study supporting approval appeared a few months ago and looked primarily at side effects and antibody response, not actual vaccine efficacy. One big caveat, the manufacturer is required to conduct post-marketing studies to ensure that vaccine recipients do not develop a worse form of chikungunya after becoming infected; this is a possibility though not highly likely. For now, I'd consider this mostly as an option for older individuals at very high risk for infection. Most other US residents should wait for further information about the vaccine, but it's good we have this option available.
This past week also saw publication of new data from Singapore about benefits to newborns of covid vaccination of mothers during pregnancy. It was a cohort study, which is a study design slightly more prone to inaccuracies than are randomized controlled trials, but it did show about 40% efficacy in preventing infection in newborns when their mothers were vaccinated during pregnancy. Of interest, pre-pregnancy vaccination of mothers was not effective in preventing newborn infection. The study covered the period from January, 2022, through March 2023. This is yet another reason to encourage covid vaccination for pregnant people, along with pertussis and RSV vaccination. The benefits do extend to their children.
Unfortunately, we also have some disappointing vaccine news in the category of missed opportunities. First, 2 studies from the CDC demonstrated poor influenza vaccine uptake by healthcare providers. In the first report, flu vaccination rates for HCP in acute care hospitals fell from 88.6 - 90.7% in the years 2017-2020 down to 85.9% in 2020-2021 and 81.1% in 2021-2022. We all know that the pandemic made it difficult to access regular health care for many people, but these are workers in acute care hospitals who didn't have that excuse. The second study looked at a broader range of HCP during the 2022-2023 flu season and showed 81.0% flu vaccination rates in acute care hospital employees and a shocking (to me) 47.1% rate for nursing home employees. Up to date covid vaccination status rates were even more depressing: 17.2% and 22.8% in acute care hospitals and nursing homes, respectively. I can understand why some people may choose not to receive these vaccines, but HCP do have a responsibility to protect those for whom they provide care. (IMHO; I'll get off my soap box now.)
Also in the Debbie Downer category, CDC reported that vaccine exemptions for kindergarteners increased for the 2022-2023 school year. The rogues' gallery includes 10 states (Alaska, Arizona, Hawaii, Idaho, Michigan, Nevada, North Dakota, Oregon, Utah, and Wisconsin) having exemption rates above 5%. Idaho easily came out on "top" with a 12.1% exemption rate. The reasons for high exemption rates are complex, note that the list of states doesn't necessarily follow political lines. States that make it more difficult for parents to apply for non-medical, aka philosophical, exemptions have lower exemption rates overall. An oldie but goodie study also stressed that exemption rates vary within a state, and small hot spots with high exemption rates can fuel outbreaks of vaccine-preventable diseases.
Missed Opportunities to Prevent Congenital Syphilis
The CDC was very busy this past week! Another report looked at missed opportunities for prevention of congenital syphilis in 2022. Looking at the 3761 cases of congenital syphilis reported that year, almost 90% of birth parents received inadequate management. This included no or nontimely testing (36.8% of parents) and no or nondocumented (11.2%) or inadequate (39.7%) treatment. I'm hoping our public health infrastructure can be shored up to lower cases of congenital syphilis, now at a 30-year high.
Tripledemic Update
Rather than showing yet another RSV-NET graph, where data are somewhat delayed anyway, I thought I'd mention a bit more about that system. It is set up in 14 states covering about 8% of the US population. Here's what the distribution and data collection looks like:
I'm not sure why (Veteran's Day?) but FLUVIEW did not update this past week, so nothing new to report there. Wastewater covid levels reported by Biobot remain lowish.
No Hasty Pudding Again This Year
I'm starting to help plan a Thanksgiving menu for later this month, and I was reminded of another ill-named item, Indian pudding. It is similar to the British hasty pudding that uses wheat flour rather than cornmeal. I have a wonderful recipe, dated 1958, from the Durgin-Park Restaurant in Boston. Durgin-Park opened in 1742 and closed in 2019, and this dessert was an icon on their menu. The reasons I won't be having it again this year are multiple but include the fact that I'm the only one in my family who likes it and that it contains about 5000 calories per tablespoon (only slight exaggeration). I think I'll just change the name to Durgin-Park pudding for future reference.
Last week I was a bit obsessed with all the leaves around my house, both on the ground and still in the trees. With a neighborhood leaf collection looming and many leaves still to fall, I decided not to rake that day. The next day I reversed my stance, which was a bad idea.
On the COVID Front
Although we aren't seeing much of a surge so far (see Tripledemic below), I did come across a few items to mention.
First, FDA issued an alert about potential dosage errors with the Moderna vaccine for children 6 months through 11 years of age. The standard dosage is 0.25 ml, but apparently the single dose vials contain "notably more" than this amount. So, if one draws up the entire contents of the single dose vial and administers it, the dose will be too high. Try as I might, I was unable to determine how much above 0.25 ml "notably more" is. So far the overdosage hasn't been shown to cause any harm. Please alert your staff to this.
On the topic of Multisystem Inflammatory Syndrome in Children, a prospective cohort study in the Netherlands suggests that MIS-C is lessening recently, possibly related to prior immunity. This fits with other reports, mostly anecdotal.
Finally, and consider this a very preliminary observation, researchers in China have noted an apparent increase in situs inversus diagnosed with prenatal ultrasound following lifting of covid restrictions in that country.
I'm advising caution in interpreting this study because 1) it is a short letter to the editor so methodologic details are a little sparse (supplementary online appendix helps); 2) funny things can happen when an epidemiologic blip is noticed that then triggers a look back - although the authors claim their protocols for performing sonography didn't change, all sorts of bias can affect the data in this setting; and 3) no one else has reported this association previously. I'm sure we'll see further refinement on this topic from these and other investigators in the coming months.
Some readers may have noticed I haven't mentioned anything about SARS-CoV2 variants for a while. They are still out there, changing rapidly as usual, but I won't comment much until/unless we see emergence of a variant dramatically different in its ability to alter epidemiology of disease, either by evasion of prior vaccine and infection immunity or with increased virulence.
New Infant Hepatitis C Screening Recommendations
CDC has issued new screening guidelines for infants born to mothers with hepatitis C, which should help identify infants at risk earlier. The entire document is very well written and informative. Expect updates to appear in the Red Book and from other organizations. Here is the bottom line for primary care providers, including a definition of perinatal exposure.
For a child not screened in early childhood:
Hepatitis C testing is a bit confusing to many providers; don't hesitate to seek assistance from your friendly neighborhood pediatric ID or GI provider!
Tripledemic Update
RSV continues, but we have yet to see any notable increases in flu or covid.
RSV-NET still shows an increase in hospitalizations nationally, ages 0-4 years shown in purple.
The FLUVIEW map is similar, though note this is tracking "influenza-like illness" which will be contaminated with other respiratory viral infections.
Biobot wastewater monitoring is at about the same level, still far below the January 2022 surge.
I continue to focus on wastewater data for SARS-CoV-2 due to the decrease and vast variability in tracking infections, hospitalizations, and deaths now compared to during the pandemic.
Autumn Thought
As I was finishing sweeping and raking leaves and carting them to the curb for pickup, a big wind came up. Within about 10 minutes, the areas I had just cleared looked exactly the same as before I started. The only change was that big maple tree outside my window now had significantly fewer leaves clinging to branches. At least I got a little exercise.
Langston Hughes, one of my 2 favorite American poets (Wallace Stevens being the other), wrote a short poem in 1921 entitled Autumn Thought:
