omicron variant – Page 7 – Pediatric Infection Connection

Marching into March

Bud WiedermannMarch 5, 2023March 5, 2023Leave a comment

Greetings and welcome to the month of March - I'm looking forward to viewing the Full Worm Moon Monday or Tuesday!

Covid Vaccine Efficacy Against Omicron in 5-11 Year-olds

Covid doesn't seem to be in the news much these days, the public is mostly tired of it. It was worth noting, however, a new report reinforcing the Pfizer vaccine's performance in this age group during the omicron era. Key points (though not new) are that a slightly longer interval of 8 weeks between 1st and 2nd vaccine doses is slightly better, though that benefit disappears after 3 months, and the vaccine provides good protection against severe outcomes for about 4 months, then starts to fade a bit. This and prior studies offer continued reassurance to families that covid vaccination, compared to no vaccination, continues to be beneficial for all age groups; the risk/benefit equation is a no-brainer.

Artificial Intelligence/Machine Learning (AI/ML) for Kawasaki Disease Management

When I was practicing full time, I'm pretty sure not a week went by that I didn't mention to someone at the hospital how much I hated Kawasaki Disease. I managed children with suspected KD for decades, mostly in the dark in terms of accurate diagnosis. The only way I could ever know if a child truly had KD is if they developed coronary artery aneurysms, and that outcome is a) present only in a minority of untreated children (thankfully); and b) really uncommon in those who were treated. We've been through multiple iterations of management guidelines, now very confusing and often requiring interpretation from an "expert." My interest in technology was piqued at seeing the words "artificial intelligence" in the title of this study. KD research in general suffers from the "garbage-in, garbage-out" problem - we don't have a true gold standard for diagnosis. For this study, the gold standard utilized for assessing accuracy of laboratory testing for KD diagnosis was the imperfect but accepted resource from the American Heart Association (AHA Guidelines). The lack of a valid gold standard for diagnosis is an unavoidable drawback in every study of KD, but with that caveat the researchers' modeling eventually came up with 3 biomarkers: C-reactive protein, NT-proB-type natriuretic peptide, and thyroid hormone uptake. Using AI-determined cutoff levels for those 3 tests, they developed a model with both sensitivity and specificity of 86% for diagnostic agreement for their patient cohorts with and without KD. (Note it does appear some of their KD patients would not have fulfilled AHA criteria, but that's another matter.)

Given the fact that KD is relatively uncommon and thus most clinicians initially evaluating children for KD do this infrequently, it would really help to have some non-subjective test result numbers to aid in diagnosis. So, this is a very important avenue of research. While 86% sensitivity and specificity sound like high numbers, they actually aren't that great in terms of narrowing down the diagnosis, particularly given that the gold standard is imperfect. I'll try not to bore you with the details of likelihood ratios, but for these numbers the positive likelihood ratio is 6.1 and negative likelihood ratio is 0.16 (the article itself didn't mention likelihood ratios, these are based on my own calculations.) Translated to the real world, if I thought a child I was seeing had a 50/50 chance of having KD based on my clinical evaluation, a positive result from the pre-test combination would raise that 50% chance to about 80%. Would I change my management based on a 50% chance versus 80% chance? Taking into account risks and benefits of treatment, I think I would treat for KD in both instances. On the other hand, if the result were negative, the 50% chance would drop to about 15%. That might be a level to maybe watch and wait, but again given the lack of a true gold standard for diagnosis I'm sticking with the existing algorithms with all their imperfections.

The authors detail how they hope to improve this model's predictive capabilities, and I look forward to seeing future studies from this group utilizing larger and better defined KD and control groups. For now, I wouldn't use this test combination outside of a research protocol.

Diarrhea in the News

I guess since covid is less newsworthy the press needed another illness for the spotlight. Diarrhea is the new poster child! A recent news story resulted in a call from one of my relatives asking how much to worry about norovirus.

Norovirus, scourge of cruise ships, is much more common in winter months. So, no surprise we're hearing about it the past several weeks. CDC reporting is mostly geared to number of outbreaks, rather than number of illnesses, so it's hard to get a handle on things. However, the outbreak number really isn't that big a deal now.

It is still a good idea to use common sense in being careful about norovirus. It is highly contagious, in part because the number of viral particles needed to cause disease is very small - about 100 or so, compared to around a billion live bacteria to be ingested to cause salmonellosis. This low "illness dose" is partly what leads to the recommendation not to rely on alcohol-based gels to protect you from norovirus and instead use the standard 20-second soap and water wash. It's not that alcohol gels (especially at a low pH) can't kill norovirus, it's more the numbers issue.

Speaking of diarrhea, another problem with low illness dose is shigellosis. Shigella infections have appeared in the news lately mainly for a problem of antibiotic resistance, termed extensively drug-resistant (XDR) strains. Usually shigellosis is a self-limited disease not requiring treatment, but antibiotic treatment can shorten duration of bacterial shedding in stool, limiting duration of contagion, and also offers some protection against severe disease which is important for immunocompromised folks and those with underlying chronic GI illnesses such as Crohn's disease.

The CDC document linked above states that only 5% of Shigella strains screened are XDR, but this does represent an increase over the past several years.

High risk groups for XDR shigellosis were men who have sex with men, people experiencing homelessness, international travelers, and people living with HIV. The total number of XDR strains was 239, and of the 232 episodes where information was complete, only 5% occurred in children. This is very different since shigellosis usually is a disease of young children. XDR strains remain susceptible to carbapenems (which would require IV therapy) and fosfomycin (oral but not approved under 12 years of age, though the drug has been studied down to newborn period). Note that the multiplex PCR packages for stool testing can detect Shigella but give no information on antibiotic susceptibility. If clinical suspicion for shigellosis is high (diarrhea containing blood and mucus, or a febrile seizure associated with a diarrheal illness), and you would consider treatment, order a standard stool culture.

Hippocrates

Yeah, that guy (or maybe a group of people) who came up with the oath. Most historians give him/them credit for first use of the diarrhea term. Of course I had to look that up, and it appears in his Aphorisms, Section VI, items 15, 16, 17, and 32. You might get a chuckle out of some of these. They seem to be in random order, but maybe there was some logic to this grouping that was more apparent in ancient times.

“Super” Sunday

Bud WiedermannFebruary 12, 2023February 12, 2023Leave a comment

Little known (and generally worthless) fact: I sold beer at Super Bowl VIII. However, it is with increasing guilt pangs that I plan to tune in to tonight's Super Bowl LVII game almost half a century later. The National Football League's highly discriminatory business practices and the medical risks to players color my appreciation of the game itself. From the medical perspective, of course it's the numerous instances of trauma more commonly involving the musculoskeletal system and brain that stand out; this year we've seen what was likely a rare instance of commotio cordis as well. Not to be overlooked, infectious diseases also have played a small role in the NFL, including an outbreak of MRSA on the then St. Louis Rams team. More on that later.

I'm happy to report nothing noteworthy in the past week's epidemiology of winter respiratory viruses, so I'll forego the usual graphs this week.

Promising New Therapy for Covid-19

Pegylated interferon lambda given as a single subcutaneous injection appears to be an effective new treatment for early covid 19 illness, according to results of a phase 3 trial published last week. About 1000 subjects received the treatment drug with an equal number receiving placebo. Subjects were at least 18 years of age, outpatients, and within 7 days of symptom onset. Most had at least 1 high risk criterion for disease progression. Eighty-three percent of the subjects were vaccinated, and the study spanned multiple variants including omicron. The active drug recipients had a 2.7% rate of hospitalization or emergency department visit compared to 5.6% of placebo recipients, which was highly statistically significant. The benefit was evident regardless of the infecting variant and the vaccination status. Treatment appeared very safe, although of course the study lacked enough participants to look for rarer side effects.

A couple of caveats as usual. This study was part of the ongoing TOGETHER trial, which has an adaptive trial design. This is a more efficient trial design method to test multiple treatments for a given condition; FDA provided guidance for this a little over a year before the pandemic began. Secondly, I was very confused by a NY Times article commenting on statements by the drug's maker referring to conversations with the FDA that could delay drug approval. What was stated in the article doesn't sound anything like what FDA regulations require, so I suspect there is more to this story than what we hear from big pharma. Still, it could signal a delay in drug availability. In general, this approach to covid treatment could be a game-changer for other infectious diseases, so I'm looking forward to more studies of interferon therapies.

New Immunization Schedules from CDC

As always at this time of year, CDC's Advisory Committee on Immunization Practices released updated immunization schedules for children and adults. It has the seal of approval from multiple organizations including the American Academy of Pediatrics. I don't see anything particularly controversial, but it does have recommendations for routine incorporation of covid-19 vaccination for all ages 6 months and above. It should be required reading not only for primary care providers but also for sub-specialists, since they need to be aware of recommendations for people with immunocompromising or other high risk conditions. Individual jurisdictions will decide how this is implemented for circumstances such as public school attendance.

More Good News on Vaccination and Pregnancy

A few new studies add more evidence for the benefits of vaccines for pregnant individuals. First, investigators from multiple countries reported that covid-19 vaccination during a time when omicron was the predominant variant significantly reduces severe symptoms, complications, and death in that population. In another study, maternal covid vaccination also was beneficial for their newborn infants, with lower rates of infection and hospitalization during the first 6 months of life.

We also have additional new data that pertussis vaccination of pregnant individuals offers significant benefit to their newborn infants. Since maternal immunization was recommended in the US in 2012, rates of pertussis particularly in the age group less than 2 months have decreased considerably. Note that this is the age group where the most severe disease and deaths have been seen in the past.

I hope those providing care to pregnant individuals will stress the benefits of these vaccines both for these individuals as well as their newborns.

Allergy Labels: Garbage In, Garbage Out

Please excuse my bias, but a study just published touched on one of my all-time pet peeves: labelling someone with a drug allergy without documenting the clinical circumstances. Often it isn't even a true allergy. This particular report looked at a sampling of children labelled as allergic to penicillin and enrolled in primary care practices affiliated with Texas Children's Hospital and Children's Hospital of Philadelphia. Not surprising (to me), the description of details of the reactions were dismally incomplete, and very few children had this label removed. However, of the children delabelled by either the primary care provider or an allergist, over 90% tolerated subsequent penicillin doses just fine. I issue a plea to all healthcare providers to not just label someone as allergic to a drug without providing a detailed description of the reaction. It makes it so much easier to assess risk of drug therapies in the future. Failure to do so sometimes results in children (and adults) being prescribed suboptimal treatments for future illnesses.

A Picture is Worth a Thousand Words

I told you I would get back to today's NFL activities, just bear with me a moment.

I have long been interested in the graphical display of information. In another part of my life, I led workshops on how to use PowerPoint and other slide presentations more effectively (short synopsis - PowerPoint was designed as a tool for advertisement, presenting a biased view, rather than to encourage critical thinking by the audience). Florence Nightingale published a terrific graph in 1858 detailing causes of death in the British military during the Crimean War. Offshoots of this graphing type are used to represent excess causes of death even today in the covid pandemic. A print of Charles Joseph Minard's map of Napolean's Russian campaign hung in my office for many years and now stares at me just beside my home work desk.

How does this relate to football? Another pretty good pictorial representation appeared in the 2005 report of an MRSA outbreak among St. Louis Rams players. Although it involved just a few players, you can see in Figure 1 how things played out. Of course, MRSA is a real problem in sports as well as in the general population. We still don't have effective preventive measures, though common sense, soap, and water go a long way in keeping everyone healthy.

The picture/1000 words title of this heading is a common aphorism that I think most of us agree is true. I had trouble pinning down the origins of this adage, variously attributed to Leonardo da Vinci, Ivan Turgenev, Henrik Ibsen, and even Napoleon Bonaparte - quite the collection of suspects. However, the credit for the verbatim aphorism I think belongs to the January 10, 1918, edition of a newspaper from my hometown. And, no, it's not a coincidence that you don't see any pictures or graphs in today's post. If you find yourself wishing I had thrown in a few, you've proved my point!

Death Valley Days

Bud WiedermannFebruary 5, 2023February 5, 2023Leave a comment

I've had a wonderful week, just returned from a west coast swing to visit a son and also do some hiking in Death Valley. In the meantime, the infectious disease world soldiers on.

Winter Virus Update

We continue to see good news from RESP-NET, though again with the concern particularly with covid that we don't have accurate case tracking, likely resulting in underreporting. XBB.1.5, as expected, appears to be sweeping westward across the country and is by far the dominant variant east of the Mississippi.

Covid Immunologic Insights

A couple of articles released recently bring up some interesting findings. First, researchers at WHO and multiple other academic institutions around the world performed a systematic review and meta-regression looking at protection from prior infection with or without vaccination against omicron infection. Not surprisingly, protection against infection itself waned very rapidly, but hybrid immunity (combination of prior infection plus vaccination) was relatively long-lasting for protection against severe disease and hospitalization: better than 90% at 12 months following last vaccination or infection. This is somewhat supportive of the proposal for annual covid vaccine boosters, although in practice it will be exceptionally impractical to determine individual prior infection status.

The other article was a detailed analysis of clonal T-cell responses to asymptomatic or mild covid infection, comparing adults and children. It is highly technical, mostly of interest to basic scientists, but I was intrigued by the finding that children did not develop effective adaptive immune responses compared to adults. This has important ramifications for future vaccine development.

More Measles Mess

We are already seeing measles outbreaks around the country, mostly isolated/contained, but given the pandemic-associated drop in childhood vaccination coverage we should prepare to see more. Now, researchers at U. Penn have reported relatively high rates of negative measles serologic testing in parturient patients at 2 Philadelphia hospitals. About 20% lacked protective antibodies to measles, an important finding not only for these patients but also for their newborns. For the babies, it's a bit of mixed news because maternal antibody will block response to measles vaccine in the first 6 months of life but also means that these infants could be unprotected very early in life. The main caveat for interpretation is that measles antibody is only a surrogate of protection from infection and thus we can't assume directly that the 20% rate corresponds to true lack of protection.

20 Mule Team Borax

I have vague memories of a television show, Death Valley Days, from my early childhood. Or, should I say what I do remember are the commercials for 20 Mule Team Borax, a laundry detergent still available today. Its main ingredient is sodium tetraborate, very toxic if taken internally or even used as a topical soak/bath. It's a sad state of affairs that I wasn't surprised that borax is yet another toxic compound advocated for use in the covid era, this time by anti-vaxxers as a bath component to reverse the effects of covid vaccination. Bad idea.

Of course, kicking up the trail dust in Death Valley, I couldn't help but think about health risks and not just from tumbling 5000 feet down the Dante's View trail. Death Valley is coccidioidomycosis territory, so if I develop a respiratory illness within the incubation period (1-3 weeks), I'll remind my physician to keep it in the differential diagnosis!

Hope Springs Eternal

Bud WiedermannJanuary 29, 2023January 29, 2023Leave a comment

An interesting week with the FDA VRBPAC meeting and release of a few new studies, but still no word from CDC on relaxing covid testing for asymptomatic individuals. Bottom line though, some more reasons to remain optimistic. Let's dive in.

RESP-NET

Trends continue downward overall as well as individually for covid, flu, and RSV in RESP-NET. This bodes well, although in the pandemic era anything seems possible. Of course still worthwhile to get flu and covid vaccines if eligible.

You might be interested to have a peek at the WHO influenza information, what is pictured below is current as of January 8. It is more or less a typical global flu picture.

As you can see, southern hemisphere activity is low for the most part, with a predominance influenza B and A H1N1pdm09 strains rather than the AH3N2 that predominated earlier. This change in strains is typical at the end of a flu season, both the B and H1N1 strains are well covered by this year's vaccine.

Covid Vaccine Horizon

As planned, the FDA VRBPAC did meet last Thursday. I was able to watch most of the day's proceedings. (It was a long day, you can watch a recording of the whole thing if you want!) Presentations by Pfizer, Moderna, Novavax, FDA, CDC, and others were followed by multiple questions and discussions, all very good. Rather than lull you to sleep with too many details, let me try to summarize key points which were all about simplification. First, the VRBPAC members voted unanimously to recommend harmonization of the covid vaccines going forward. By that I mean that each manufacturer will be providing the same vaccine for both primary series and boosters. So, we won't need to worry about whether a monovalent or bivalent vaccine is needed for a particular individual. If the FDA follows these recommendations and CDC/ACIP agrees, only the bivalent vaccines will be used for primary and booster series - we won't be able to access the monovalent mRNA vaccines. I certainly concur with this - we have had so much lost in translation in implementing covid vaccination in the US, it is too confusing for providers and vaccinees - and data are very reassuring that the bivalent mRNA vaccines have an excellent safety profile and at least equivalent efficacy, if not a little better. More on that later.

Not to be forgotten, we have a third vaccine from Novavax also authorized in the US. It is an adjuvanted vaccine that does not involve mRNA technology, and studies have shown excellent safety and efficacy in adults. Pediatric studies have lagged considerably and the company did not present any substantive new data for young children.

What remains confusing still is how individuals with prior infection but no prior vaccination will be treated. Probably one dose of vaccine would suffice, but how do we verify prior infection for an individual? Also, how do we determine exceptions to what could be a recommendation for annual covid vaccination for most people? Those exceptions include elderly, immunocompromised, and perhaps young children. Will some of them be recommended to receive 2 vaccines per year? Although this is a move towards simplicity, none of this is easy, and the devil will be in the details. I hope the CDC and other agencies are up to the communication task.

Expect more updates on timing and composition of vaccines to be available in late summer/early fall. Churning out an mRNA vaccine targeting newer variants takes about 100 days, maybe a little longer for the Novavax vaccine. It looks like the VRBPAC will be meeting again around May. We should all be very thankful for the efforts of VRBPAC staff and committee members.

Advice for Immunocompromised

Speaking of communication (pun intended), CDC has a nice graphic and somewhat clearer guidance for immunocompromised folks.

This definitely helps, but we all know that not all immunocompromise is equal, so the vaccine nuances (especially whether to administer subsequent doses once or twice a year) will be tough to explain for those with milder underlying conditions.

New Studies of Bivalent Covid Vaccines

Last week saw publication of three updates of results of bivalent covid boosters; all were discussed at the FDA meeting. First, a group at the University of North Carolina reported state data suggesting bivalent vaccine efficacy was pretty good against some of the newer omicron variants. The bivalent boosted individuals (study included ages 12 years and up) had better protection against severe infection than did those who received the monovalent booster. However, numbers were small resulting in wide confidence intervals, and as always protection lessened with longer time after boosting.

CDC reported early estimates of bivalent booster protection against BA.5 and XBB/XBB.1.5 sublineage variants in adults. The study had the same caveat about small numbers and wide confidence intervals, but again a suggestion that the bivalent booster might be performing better than the monovalent booster for these newer omicron variants.

Finally, a study just looking at the Pfizer vaccine showed somewhat better serum neutralization activity against the newer variants in adults who received the bivalent booster compared to those who received just the monovalent booster. This is an important study but less helpful since it is looking at a surrogate marker (neutralization levels) rather than true vaccine efficacy.

More Good News About mRNA Vaccines in Children

A large meta-analysis published last week provides more information about the excellent safety and efficacy of covid mRNA vaccines in children in the 5-11-year-old age group. Benefits far outweigh any risks from these vaccines.

Vaccine Conversations: AAP to the Rescue

The American Academy of Pediatrics published a 49-page report on methods for productive discussions of vaccines with families. If you don't have time to wade through that, AAP will have a 1-hour webinar this Thursday, February 2. I don't think you need to be an AAP member to attend.

Hope

The line "hope springs eternal" is buried somewhere in Alexander Pope's poem An Essay on Man. I also learned that it was the title of a 2018 indie film. I'm not planning to look into either Pope's poem or the movie. However, I can recommend the book I'm reading now, Sea of Tranquility by Emily St. John Mandel, especially if you've read any of her earlier books. It's contains a story of a fictional pandemic, but since I haven't finished it I don't know whether the ending is hopeful or not!

Another Week in the ID World

Bud WiedermannJanuary 22, 2023January 22, 2023Leave a comment

A few interesting items last week. I also enjoyed the CDC COCA call on Saturday - not much new stuff, but a nice summary of issues surrounding covid variants and immune escape among other topics. The recording should be posted soon. It was mostly geared towards adult care.

Tripledemic Receding

I made a great (for me) discovery of RESP-NET - I'm not sure if it is new or if I just wasn't aware of its existence, but it tracks the 3 viruses of interest all on one page. Here is the most recent view:

This is an interactive graph, note on the left side and at the top there are multiple views. The age group 5-17 years is selected here and you can see that downward trends are present for combined respiratory virus-associated hospitalizations as well as for influenza and RSV. Covid doesn't have a consistent downward trend but the recent data (which may be affected by reporting delays) also is heading down. Let's hope so.

Vaccine Coverage

CDC just started reporting covid vaccine rates for children under 5 years of age. It's not pretty and is similar for all ages.

Again, this is an interactive graph, so you can look at rates by sex and age.

A Brief Word on Variants

Here is the latest. Also, I may not have mentioned this before, but if you look at the top right the NOWCAST designation for the past 3 weeks indicates this is a forecast, not based on data collected those specific weeks. The variant data always have a lag time to allow time for sequencing to be performed. For example, the latest actual data we have on this graph is for the week ending December 31, 2022.

Are you starting to get too confused about variant nomenclature? I am. As a quick review, the original omicron variant that appeared in 2021 was BA.1. In January 2022 it was mostly replaced by BA.2. Subsequently we've seen new omicron lineage variants labelled BA.3, BA.4, BA.5, and XE.

The variants taking over in the US now are labelled XBB and BQ.1 and are descended from the BA.5 sublineage. (XBB is a recombinant of BA.2.10.1 and BA.2.75 sublineages, not to confuse you more.) XBB has a high level of immune escape (i.e. immunity from vaccines and prior infection is lessened and current monoclonal antibody therapies are less effective) and also probably enhanced binding to the ACE2 receptor on our cells.

On the other hand, it appears that BF.7 is circulating now in China - this is a sublineage of BA.5 that hasn't taken off in the rest of the world so far.

Wastewater

Wastewater is a very important source of data on what variants are active and when we might see covid surges. Unfortunately I don't think the CDC data presentations for wastewater are very helpful, and the data sources are scattered sporadically throughout the country. This is because reporting has been on a voluntary basis; if you live in a blue state area, you have a better chance of early alerts from wastewater testing. Several national agencies are working on a better network for wastewater testing, but the legal and ethical issues are significant. For example, one could also choose to test collection sites for drugs of abuse and then target police actions to a specific region - those working on a better process want to restrict wastewater testing to just public health uses that do not stigmatize or otherwise target communities for other reasons. I attended a nice summary of the situation provided by the National Academies of Sciences, Engineering, and Medicine (NASEM) which is studying the issue and has produced a preliminary report.

Is My Spice Rack Going to Kill Me?

No, but the closest I come to hoarding behavior is my spice armamentarium. I did a quick count and noted 105 unique spices in my kitchen cupboard, and that doesn't count the maybe 40 or so extra large bags plus maybe 6 different kinds of salt I have on hand.

Last week the lay press picked up on a study that first appeared last September. It looked at contamination rates for people making turkey patties and lettuce salad. The participants were told they were evaluating new recipes, but in fact the turkey meat was laced with a harmless bacteriophage that was then tracked to see where it ended up after the food preparation. It turned out the spice jars were a prime source of contamination. The study didn't seem to address the amount of contamination, but at least it should serve as a good reminder that hand and dish washing during food preparation should be thorough.

I don't plan to wash all of my spice jars, as you might imagine I'm a stickler for food hygiene when I'm cooking!

Fear the Snail

Well, not really. But a recent issue of the Journal of Infectious Diseases reported new trematodes found to be carried by snails in California and elsewhere. These agents have the potential to infect humans, with transmission most likely in a manner seen with angiostrongyliasis in Hawaii. Bottom line, don't eat raw snails on a dare (yes, some people have done this and become infected), and make sure your produce is washed well - you never know when a snail has slimed its way across that piece of lettuce.

Looking Forward to This Week

CDC will release new guidelines for covid testing that will likely de-emphasize routine screening of asymptomatic individuals. The draft is being reviewed now, so expect something fairly soon, perhaps this week.

Also, FDA/VRBPAC will meet on January 26 to start planning covid vaccine strategy going forward. As of today (January 22) the agenda still has not been posted but "the discussion will include consideration of the composition and schedule of the primary series and booster vaccinations" for covid vaccines. I plan to listen in though I don't expect any final decision to be made at this meeting.

Tag: omicron variant