December 2022 – Pediatric Infection Connection

Happy Holidays

Bud WiedermannDecember 25, 2022Leave a comment

Whether you celebrate Christmas, Hanukkah, Kwanzaa, or any number of winter solstice/festival of light ceremonies like Saturnalia, Dong Zhi, Sah-e Yalda, or Shalako (the list of holidays this time of year is quite long), or choose to celebrate nothing at all, I hope you will take advantage of a few days away from work to relax and reflect.

Tripledemic Tracking

Let's check the latest stats from CDC.

RSV

The hospitalization rate graph looks pretty similar to last week on RSV-NET, the final endpoint is for data ending December 17. As indicated in the inset, recent data likely suffer from reporting lag. Still, overall good news.

I'm hoping our community of RSV-susceptible individuals is very low now, such that we won't see a rebound later. Note that we usually have 2 strains of RSV circulating every year, RSV A and RSV B, so in theory it is possible to be infected twice in a season. In the past this has occurred only rarely.

Influenza

Influenza likewise continues to decline nationally as per FLUVIEW, though still at a high level.

The lay press has a lot of buzz about flu increasing because of holiday travel, but I'd remind folks that sometimes with early flu seasons in the past, we've actually seen a big decline in infections because kids are out of school. Again, still plenty of flu around, and with 3 strains circulating still important and not at all too late to get vaccinated.

COVID-19

The CDC's weekly data update is on holiday, but daily updates occurred last on December 23 and I could access a graph similar to last week that tracked through December 21.

Rates continue to increase in general. If you aren't already, indoor masking would be prudent now. I continue to be appalled by the low booster vaccination rates in people who have already received the primary covid vaccine series.

Invasive Group A Streptococcal (iGAS) Infection

I've been following this topic in my myriad of listservs since early reports appeared from the Netherlands last spring, but now the lay press has raised an alarm likely in response to CDC weighing in. The problem is still very uncommon and only sporadically cropping up, but it's worth reviewing what's going on.

CDC issued a Health Alert Advisory (HAN) on December 22 documenting increased reporting of iGAS cases this fall; these include entities such as scarlet fever, cellulitis and necrotizing fasciitis, mastoiditis and sinusitis, retropharyngeal abscess, pneumonia/empyema, and streptococcal toxic shock syndrome. What isn't clear is whether this is something unusual or just the expected number during streptococcal season in a year when we are back to mostly "full contact" among people in our communities. Certainly the large number of respiratory viral infections bear some blame; iGAS is well known to follow viral infections. A few clinical caveats for healthcare providers as well as parents:

A biphasic illness, meaning a respiratory infection/fever followed by a few days of relative well-being and then return of illness with high fever and other symptoms, is a classic red flag for bacterial superinfection following viral illness. That is a time to seek care and pay close attention to consideration of iGAS.

Streptococcal skin infections occur much less frequently since the advent of varicella vaccine. But, given the drop-off in regular childhood vaccines, we likely have a much larger group of children non-immune to varicella. Beware iGAS superimposed on varicella.

Group A streptococcal pneumonia and empyema can be severe. Back in my days as inpatient teaching attending I referred to this as Henson's disease (not to be confused with Hansen's disease, aka leprosy) because this is what killed puppeteer Jim Henson. (I note that his Wikipedia entry has a confusing entry about his final illness, including blaming Disney negotiations for his illness!)

Necrotizing fasciitis is especially dangerous. It is a deeper skin and soft tissue infection than is simple cellulitis and can progress very rapidly to cause extensive tissue destruction and death. One possible clinical clue for healthcare providers is that the degree of pain at the site seems out of proportion to the skin appearance. Quick intervention with both antibiotic therapy and surgical resection can be life-saving.

Speaking of antibiotics, pediatric healthcare providers are aware of the amoxicillin suspension shortage nationwide, ongoing for many months now. AAP has a nice list of alternatives.

Cherish Diversity

Too often recently, the cultural and other differences among us are used instead as excuses for persecution. Wouldn't it be nice if we could all just cherish our diversity and use it to build rather than tear down communities? Have a wonderful holiday of your choice!

Potpourri

Bud WiedermannDecember 18, 2022December 18, 2022Leave a comment

It's that time of year for various types of potpourri, either simmering on the stove or in dried form. I also realized a need for my own infection potpourri, I have so many topics to catch up on. Here goes.

The "Tripledemic"

You wouldn't know it from the news, but there is reason to be optimistic now even with covid cases surging.

RSV

RSV isn't a reportable disease in the US, so accurate tracking is tough. However, CDC's RSV-NET utilizes active reporting from 58 counties in 12 states (CA, CO, CT, GA, MD, MN, NM, OR, and TN) to give a partial picture:

The above is just one screenshot of many in this interactive display, but note the green bar representing the 2022-2023 season. It confirms what pediatricians in our area have been seeing for the past few weeks - RSV is way down. This needs to be tempered with the fact that current hospitalization rates now are in the same ballpark as peaks in the 2 prepandemic years, so there's still a lot of disease activity.

Although there is no guarantee we won't see another peak later on this winter, I would doubt it. We have probably run through the bulk of susceptible young children, so the remainder will be children born in the next few months. If their mothers were infected in this round, these newborns (except for the extreme prematures) will have benefit of maternal antibody. Also remember that, if studies go well, RSV vaccination for pregnant women and a longer-acting monoclonal antibody preventive treatment may be authorized or approved in 2023. (You can see I'm carried away by optimism today!)

Influenza

Similarly, we might be seeing a break in flu nationally, though like RSV and all other respiratory viruses, the disease activity can vary widely in different parts of the country. FLUVIEW shows us the picture from a few different angles. First is influenza-like illness, which can include other respiratory viruses besides influenza because it has a clinical definition without requiring diagnostic proof of influenza infection:

Note there is a clear downward trend for the (red) 2022-23 season, but also compare with the (green) 2019-20 season with multiple spikes that likely reflected the beginning of covid. However, there is additional evidence to suggest flu is waning when looking at the hospitalization rates for confirmed influenza (also from FLUVIEW).

The slope of red line, which shows cumulative hospitalization rates, is decreasing. Keeping fingers crossed, but still plenty worthwhile to get a flu vaccine for those who have procrastinated. We still have a ways to go with flu this winter.

COVID-19

Poor reporting of at-home test results and general apathy about all things covid mean our data aren't as reliable, but we're certainly seeing a surge this winter which is entirely expected.

The telling parts of the graph above are not only the somewhat tiny blip in weekly cases but more significantly the sharp increase in percentage of positive tests that likely spells at least a modest covid winter.

I'm hoping this winter won't look anything like last winter, but as usual it will depend on the variants.

The omicron subvariants BQ.1, BQ.1.1, and XBB will guide the next few months. They have certain advantages in terms of immune escape and growth but so far do not seem to be causing more severe disease. Human behaviors such as vaccine hesitancy and not restricting activities when having respiratory symptoms also are significant determinants for what the winter holds.

New MIS-C Case Definition

Along the lines of more good news, MIS-C has become increasingly uncommon in the omicron era.

Even last winter, MIS-C was not as common as in previous waves, and this trend is continuing now. The exact reasons aren't clear, likely a combination of previous infection, vaccine immunity, and perhaps genetics of the variants themselves. CDC recently modified the case definition to make it more accurate and easier to report; this will take effect in 2023. Check out a CDC webinar for the graph above and more information about MIS-C.

A More Accurate View of the Global Burden of the Pandemic

So, some degree of good news for covid. However, the overall status still is depressing. WHO estimates the cumulative burden of the pandemic to be almost 15 million excess deaths. Although we've all become somewhat numbed by large numbers, take a moment to let that sink in.

On the good news side, the Commonwealth Fund has estimated tremendous benefits from the first 2 years of covid vaccination in the US:

Covid Vaccine Updates

Speaking of covid vaccines, a few new items appeared recently. CDC released 2 reports showing relatively good efficacy of the bivalent boosters in preventing serious disease in adults. The studies are still preliminary and have a lot of limitations including not being able to control for individual behaviors such as use of therapeutic options like Paxlovid. One study looked at hospitalization rates in those 65 years and older and the other reported emergency department, urgent care, and hospitalization rates in immunocompetent adults.

One study of the Pfizer vaccine documented the benefit of booster dosing in the 5 - 11 year-old age group. This was during the delta and omicron periods but before the bivalent booster appeared.

Now we just need to improve our dismal covid vaccination rates! The AAP provided a guide for busy practices trying to figure out which vials to use for which circumstances, and CDC provided a nice webinar (I learned several things) about discussing vaccine hesitancy. I urge all healthcare providers to look at it.

Happy Birthday Louis!

Whenever I spoke about ancient (i.e. older than 5 years) history of infectious diseases, trainees always assumed I was speaking from personal experience. Let me be clear: Louis Pasteur was not a contemporary of mine. A very happy 200th birthday to Louis on December 27. Several editorials in the December 17 Lancet marked this milestone. The proponent of the germ theory of disease and developer of the first rabies vaccine likely could still teach us a few things about handling today's pandemic.

Also, I can't leave the subject of birthdays without noting my wife's birthday this week. She is considerably younger than Louis. Happy Birthday to Pam!

Covid Milestones?

Bud WiedermannDecember 11, 2022December 11, 2022Leave a comment

Last week the New England Journal of Medicine published a perspective announcing a milestone in the pandemic. Also, we reached another milestone of sorts with the authorization of bivalent covid vaccines down to 6 months of age. I think the milestone designation is a bit overhyped, but the topics are worth exploring.

Vaccine Correlate of Protection (CoP)

The NEJM blurb's title was a bit misleading, saying this milestone had been attained. It depends on how you define CoP, but at this point we don't have an antibody or other cutoff that anyone can point to as a true CoP. The authors acknowledge this in the text. It's worth thinking about what we have so far and what barriers we face in finding a true CoP for covid.

Healthcare providers pretty much know that multiple measures of immune response can be analyzed, but it's quite a challenge to figure out which of those measurements correlate with protection. It is clear that both serum anti-spike IgG antibody and anti-SARS-CoV-2 neutralizing antibody titers correlate pretty well with protection from infection and illness; the higher the titer, the less likely the outcome will occur. However, there is still no specific number to predict with reasonable confidence that an individual is protected from a specific outcome. The reasons (and barriers) are multiple: 1) covid is a respiratory mucosal infection that can be invasive into the bloodstream - mucosal antibody might be a better target for a CoP, but that is a much more difficult set of circumstances; 2) antibody levels decline after vaccination, so an individual's titer at one point in time is going to fall fairly quickly; 3) assays have been performed in different labs with slightly different techniques - the lab methods need to be standardized going forward; and 4) the current CoPs were obtained primarily from data on previously uninfected subjects who received anti-spike vaccines before omicron and even delta variants had appeared - sort of a moving target or wack-a-mole problem we've faced with covid all along.

All this aside, even the current CoPs are extremely helpful to evaluate and approve newer version of covid-19 vaccines.

Bivalent Vaccines Authorized for Younger Children

FDA has authorized, and ACIP recommended, that both Pfizer and Moderna bivalent vaccines now be used for booster/third dosing in children starting at 6 months of age. Details are available at the linked websites. The endpoint for the current authorization is age 5 years for Pfizer and age 6 years for Moderna, just because of different age cutoffs used for the original vaccine trials by the 2 companies. The wording is a little confusing due to the nature of prior authorizations of the monovalent vaccines.

Moderna's monovalent vaccine was originally authorized as a 2-dose series based on immunogenicity, safety, and efficacy data in children ages 6 months through 5 years. Thus, the Moderna bivalent vaccine is designated as a booster dose to be given at least 2 months after the 2-dose primary series is completed.

Conversely, the Pfizer dose is not a booster, but is considered part of a 3-dose primary series. Pfizer's original studies of the monovalent vaccine in this age group did not meet immunogenicity targets in the 2- through 4-year-old age group and thus was eventually authorized as a 3-dose series for the 6-month through 4-years age group.

Don't let this confuse healthcare providers or families. Essentially both Pfizer and Moderna dosing should be considered as a 3-dose package. Whether the third dose is called part of the primary series or a booster shouldn't matter in practical terms. I'm hoping CDC and ACIP will clarify this in their online materials for families.

I don't see any compelling reason to favor one product over the other in this age group, I would just recommend choosing whichever is more convenient to obtain. A bigger problem is the extremely low vaccination rate in this population. (You will need to click the "Age" tab in the first graph section to see the data.)

Who Cares About Milestones Anyway?

In a relatively short time I will achieve what some people call a milestone, becoming a septuagenarian. I don't plan on feeling any differently. For this whole milestone thing, I can only say, Bah! Humbug!

Collateral Damage 2

Bud WiedermannDecember 4, 2022December 4, 20222 Comments

Of course covid hasn't gone away, we are entering a period of increased activity in the US now. (Note that reported new cases showed a slight decline, but hospitalizations are up; this likely reflects poor reporting of new infections.) If no new significantly different variants emerge, I don't think we'll see anything like last winter's covid surge. Individuals can now report home test results anonymously; if used extensively it would provide better understanding of disease activity.

Unfortunately immunocompromised and other high-risk individuals will need to weather this covid winter without much help from monoclonal antibody treatment and prevention strategies. Bebtelovimab is now unavailable for treatment due to poor neutralizing activity against current variants. Tixagevimab/cilgavimab (Evusheld) still is available for preventive management in very high-risk people due to lack of any other effective pharmacologic preventive measures, but Evusheld also is likely to be ineffective for the current variants.

Increasingly now our attention should also focus on what I call collateral damage, mainly through 2 mechanisms. First, the pandemic disrupted other respiratory virus transmission during its peak, meaning a lot of young children haven't seen our common respiratory viruses in their lifetimes. Also, a number of factors combined to lower general immunization rates across the globe. So, we have a large collection of non-immune people, including young children, at risk not only for covid but also for both common and previously rare (in high resource countries) infectious diseases.

The Mother of All Flu Seasons?

Well, no, but it's been tough and may last a bit longer. I haven't seen a flu map this bad in a long time (late October 2009, our pandemic year, is in the neighborhood; you can scroll back to see it at the same weblink).

Note that this map represents "influenza-like illness" activity, so likely includes some RSV and other respiratory infections as well.

Most of the influenza cases currently are H3N2 which is well-matched by this year's vaccine. It's still wise to provide flu vaccine to unimmunized children even if they have already had a documented influenza infection because both the 2009 pandemic strain of H1N1 as well as influenza B strains also are circulating and likely will increase later in the season. Olsetamivir is helpful for treatment of high-risk children with flu.

Be on the Lookout for Previously Rare Vaccine-Preventable Diseases

Measles probably represents our biggest risks for outbreaks and deaths worldwide, because of high transmission rate and severity of disease. It won't take much to see outbreaks in the US. Also, did you know England has already seen a diphtheria outbreak this year? The US is at risk as well. Pertussis is always around and could be more severe in the coming months; also watch out for more cases of otitis media (if poor pneumococcal vaccine rates), tetanus, and, as we've already seen, polio.

You Can Limit Collateral Damage

Pandemics and other times of upheaval have always affected immunization rates. However, I am struck by the degree of anti-vaccination campaigns and general misinformation we've seen in what should be an era of enlightenment and celebration of vaccine successes in the US. Frontline healthcare providers are an important countermeasure against this collateral damage. Don't miss an opportunity to reinforce this with your patients and families.

Month: December 2022