group A streptococcus – Pediatric Infection Connection

I tried, but not hard enough, to ignore the drama in the House of Representatives this week. At least now we can step back for a bit before we find out what the House looks like when the dust clears. I hope we still have a somewhat functional legislative branch of government.

This past week characteristically is the least reliable in terms of public health epidemiology. This is because our winter holidays naturally result in some delayed data collection and reporting. Even with likely under-reporting, the covid map doesn't look too good. Rather than boring you with unreliable numbers today, instead I will focus on a question about last week's blog.

Flu vs. Covid

Last Monday Michael Schwartz asked 2 questions:

1. Why do we continue to pursue universal testing and recommend isolation for a minimum of 5 days for COVID , but do neither for influenza ?
2. Should we be trying for universal testing and longer isolation for influenza or should we be treating COVID as endemic and treat it like influenza , or some other answer ?

We still have many questions left unanswered, but it may be that covid could become more like influenza in terms of disease management. Influenza and SARS-CoV-2 are both RNA respiratory viruses, but they have significant differences. Still, the history of influenza pandemics might help inform the path forward with covid.

Not much is known about flu pandemics in the 19th century, mostly because the science and reporting wasn't well-developed at that time. Subsequently our flu pandemics all have been influenza A, because it is able to change and "jump" from one species to another. Influenza B does not have an animal reservoir outside humans, plus it is well adapted to us, so it basically behaves like a regular seasonal flu virus rather than causing pandemics which require a large non-immune population. (Note there is an influenza C virus group, but relatively little is known about its epidemiology. Mostly it just doesn't cause problems, which is why most people have never heard of influenza C.)

Everyone knows something about the 1918 flu pandemic, caused by an A H1N1 subtype that jumped from animals to humans. About 40 million deaths occurred worldwide. The next flu pandemic was in 1957 with an H2N2 subtype that had some leftover elements of H1N1 combined with a bird strain of flu. It was a bad time, estimated several million deaths, but not on the order of 1918. With the start of the H2N2 pandemic, circulation of H1N1 flu went away for awhile and just H2N2 persisted as the main seasonal influenza A strain circulating.

Then we experienced an H3N2 pandemic in 1968, but it shared some elements of the 1957 H2N2 strain so not as severe. I have no memory of a pandemic in 1968 even though I was a teenager and thus partially sentient. (Certainly other historical events that year occupied my attention.) H3N2 persisted as seasonal flu, but in the late 1970s H1N1 reappeared as another seasonal A strain. This setting remained until 2009 when we had our most recent flu pandemic of H1N1, a pretty complex reassortment from human, pig, and avian strains. It was actually somewhat similar to the 1918 strain that persisted for a while, so the elderly didn't have as much problem with the 2009 pandemic as might have been expected. Also, folks like me who received the 1976 "swine flu" vaccine (I do remember all that kerfuffle at the time) also had some leftover immunity active against the 2009 H1N1 strain.

All of us should be getting annual flu vaccines, mostly to guard against the common minor changes in circulating flu strains (antigenic drift) as well as to control the relatively uncommon major changes (antigenic shift). SARS-CoV-2 also has minor and major changes ongoing, but the biggest difference is that so far they both occur much more frequently than for influenza. Ergo our moving target or "whack-a-mole" strategies with vaccines and monoclonal antibody treatments the past couple years.

Here are some other comparisons, assuming normal hosts:

	Influenza	SARS-CoV-2
Incubation period	2-3 days	~3 days¹
Reproduction number	1.3-1.7 (seasonal)	?²
Asymptomatic rate	5-30%	>40%³
Duration of contagion	1 day before - 5-7 days post symptom onset	2 days before - > 5 days post symptom onset⁴

All SARS-CoV-2 estimates are highly variable.

¹Varies with viral variant, prior SARS-CoV-2 immune status, age

²Widely variable based on multiple factors

³Varies with age and prior SARS-CoV-2 immunity, still not well established

⁴Varies with multiple factors including disease severity

Lots of footnotes and disclaimers, but perhaps you'll agree there are similarities between flu and covid. If SARS-CoV-2 does progress to behave more like a seasonal respiratory virus, we will be managing it more like we do flu: annual vaccination with composition determined by the most recent variants and (I hope) avoiding school and work attendance when ill, plus lessening of the mandatory testing and quarantine guides still in effect. Of course, if we do veer off to another major variant change that demonstrates increased severity, we are back where we started (except with a now pandemic-exhausted public). Time will tell, but I'm hoping we soon will revert to Michael's second option of settling into an endemic response mode.

More on Invasive Group A Streptococcal Infections (iGAS)

A couple of reports in the online journal Eurosurveillance offer a bit more information. British authorities describe the pattern of iGAS in children over the past few years, clearly showing an increase in absolute numbers. No specific emm types (the gene coding for specific M proteins that could confer enhanced virulence) were identified. The investigators document some association with respiratory viruses such as human metapneumovirus and RSV, but it isn't clear that this is significant since it is the season for both streptococcal infections and many respiratory viruses. In the Netherlands, investigators describe iGAS cases in children, particularly streptococcal toxic shock syndrome and necrotizing fasciitis. The latter showed an association with varicella infection, a known risk factor. Again, no specific emm type jumped out. In retrospect, it seems odd to me that the British study didn't even mention varicella co-infection.

Neither of these studies involved a control group looking at viral co-infections, so it's still hard to know what's behind these trends. The one potentially modifiable factor for prevention is varicella immunization.

1968

If there was a time period that forever changed the type of person I am, it was probably this year. I find it mildly amusing that I have no memory of the flu pandemic, clearly I was distracted by the Tet offensive, the tragic assassinations, the Democratic convention, Smith and Carlos at the olympics, and even the pictures of Earth from Apollo 8. My fascination with infectious diseases was yet to come.

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!