May 2022 – Pediatric Infection Connection

Treading Water

Bud WiedermannMay 29, 2022Leave a comment

Although schools aren't quite out yet, the weather is warming up and it's about time to think about relaxing in a pool or at the beach somewhere. I feel a little bit like we're treading water with respect to COVID-19 in the US, waiting to see what how our new omicron subvariants behave, how much the holiday weekend will bump up cases, and whether the upcoming FDA review of evidence for vaccines in the under-5 and -6 year-olds will result in the long-awaited authorization for young children.

Two Views of Disease Transmission

Recent lay press statements and comments from some of my colleagues alerted me to the fact that many may not be aware that the CDC has 2 tracking tools for measuring disease activity. Mentioned most often is the COVID-19 Community Level. This is directed at communities to help track if the infection rates are becoming severe enough to strain healthcare resources. It first looks at new cases in the past 7 days, whether below or above 200/100,000 population by county. It then looks at new hospitalizations and percent of staffed inpatient beds occupied by COVID-19 patients, with different cutoffs based on the new case count partition. The numbers are boiled down into Low, Medium, or High levels, though if the new cases are >200/100,000 population the minimum level is Medium. Guidelines for prevention strategies are then provided for individuals, households, and communities based on the Community Level.

Here's the big picture (weak pun intended):

Things don't look great in the DMV region right now, but of course this is a very fluid situation.

Contrast this with CDC's Community Transmission Levels. You can see right away one source of confusion, this term is very close to Community Level above, but it's a different calculation for different purposes. This measurement is targeted specifically to help healthcare facilities, not for the communities at large. Levels are categorized into Low, Moderate, Substantial, and High based on new cases per 100,000 persons in the past 7 days (<10, 10-49.99, 50-99.99, and >100) and percentage of positive nucleic acid amplification tests in the past 7 days (<5%, 5-7.99%, 8-9.99%, and >10%). The higher of the 2 determinations determines the Community Transmission Level:

As you can see the 2 measurements have very different views for how things are going, but neither bode well for our DMV area.

Which Eligible Kids Should Receive Vaccine Now?

This is in part an answer to Michael Schwartz's question to me last week. All frontline pediatric healthcare providers are being asked what to do about vaccinating children now. From my viewpoint, it's a very simple answer, but the sticking point is how to communicate options to parents and children particularly if they aren't accustomed to weighing choices in medical care. From a risk/benefit perspective, one needs to weigh that ratio in 2 scenarios: getting the vaccine versus being infected. For the primary series in all age groups, it's not even a close comparison. The risks associated with vaccine are miniscule compared to being infected, even for a healthy child. The magnitude of those risks is at least 100-fold different. What makes it a little tougher is that the absolute risk of complications from infection is much lower in a healthy child than, say, for an old geezer like me. So, I can see where the hesitation by some parents originates.

The question of a booster dose, now authorized for the 5-11 year-olds, might take a bit more analysis. Again, we have tremendous reassurance about side effects, so it's more about benefits and timing of the booster. With the newest omicron subvariants now dominant in the US, no vaccine is particularly effective against infection itself, but benefit remains (if we can transpose from studies in older populations and in other countries) for prevention of symptomatic disease and need for visit to a healthcare provider. It's important for parents to consider individual circumstances such as high-risk contacts their children might have with grandparents, etc. If these kids are to receive a booster, now is a good time since nothing new is likely to be available until the fall at best.

I might add, in my broken record mode, that the press releases from vaccine manufacturers giving a preliminary vaccine effectiveness number are way too preliminary. The confidence intervals are huge, and also I would not base any decision on partial data reports from an entity with an overwhelming implicit bias in seeing their vaccines authorized.

COVID Information Fatigue? Check Out These 2 New Outbreaks

Bud WiedermannMay 22, 2022Leave a comment

Good news this past week with FDA authorization of COVID-19 boosters for the 5-11 year olds, but don't take your eye off the more important issue of improving the primary vaccination series rate for this age group, currently sitting at a dismal 28%. An important take home from the ACIP meeting was continued evidence that the vaccine is safe in this age group with overall lower rates of myocarditis compared to adolescents and young adults. I'm still waiting optimistically for next month's meetings about vaccine in the youngest age groups.

In the meantime, my attention increasingly is focused on new outbreak developments.

Monkeypox

In the late 1960s/early 1970s I had the amazing good fortune to spend a few summers working in a world-class virology research center, undoubtedly sowing the seeds for my future interests. I was basically a glorified research assistant helping a veterinarian studying herpesviruses, but I was also surrounded by other labs dealing with mysterious (to me, at the time) organisms. The monkeypox facility was nearby, a high level biosafety lab that required me to don full Andromeda Strain garb when I went in to borrow equipment.

Monkeypox, an orthopoxvirus and cousin to smallpox, usually occurs in residents in or travelers from the West African and Central African countries where it is endemic. Cases turn up in the US sporadically. However, now we are seeing small clusters of infected individuals turning up in many different countries - Spain, France, Belgium, Germany, Italy, Sweden, Portugal, UK, Canada, US, and Australia so far. We haven't seen anything like this before and it is likely we will see many more cases around the world. Current affected individuals have been predominantly young men with an overrepresentation of men who report sexual contact with other men. Early testing suggests these cases may involve the West African strain which has a lower mortality (about 1%) compared to the Central African clade (up to 10% mortality). An antiviral medication, tecovirimat, has FDA approval for treatment of smallpox and likely would be effective against monkeypox; the approval was based in part on animal studies of monkeypox. Vaccines against smallpox and monkeypox are likely to be effective in preventing disease, though I doubt we'll need that option in the US. Monkeypox is not highly contagious, it requires close contact. However, if you think you are dealing with a case, institute full infection control with gown, gloves and N95 mask protection while you are calling for assistance.

Monkeypox infection is fairly distinctive, usually with systemic symptoms of fever, chills, lymphadenopathy, and a vesicular or pustular rash. It may be confused with secondary syphilis, HSV, chancroid, or varicella zoster infection. The CDC website is useful. If you think you might be dealing with a child or adolescent with monkeypox, call me (or your nearest pediatric infectious diseases specialist).

More on Severe Hepatitis Cases

Investigations are ongoing attempting to uncover the etiology of clusters of severe hepatitis in young children in the US and worldwide. CDC provides weekly updates. Since I mentioned this last week, we don't have any breakthroughs yet. However, I've been working on a guide for clinicians to facilitate identification and evaluation of cases. I offer what I have so far to aid in evaluation at the front lines of care in office practices, urgent care, and emergency departments.

First, I made up a name for this: Pediatric Hepatitis of Unknown Etiology (PHUO). Certainly someone more clever than I will come up with a better acronym. Potential cases (termed Person Under Investigation, or PUI) currently are defined as children under 10 years of age with AST or ALT >500 U/L. If you are dealing with that, it's time to consult with a subspecialist, but the issue is how to get there in an efficient manner without testing every child who vomits once or twice. To do that, it's helpful to know what cases so far have looked like.

In a cluster of 9 cases of PHUO in Alabama, common symptoms were emesis (78%), diarrhea (67%), fever (56%), and fatigue (44%), with small numbers of upper respiratory symptoms, poor appetite, and dark urine. On exam, icterus/jaundice was present in most (89%) and hepatomegaly in 78%, with splenomegaly and hepatic encephalopathy also noted at presentation in small numbers. A detailed report from the United Kingdom noted similar numbers and mentioned pale stools in 50% of 450 cases under investigation. Two-thirds or more of the children in Alabama and the UK were under 5 years of age.

As you may deduce from the percentages, children seldom exhibited just one sign or symptom; multiple were present. A frontline provider evaluating a child with a compatible clinical picture as above should obtain further history for travel, environmental exposures (e.g. pesticides), family history of liver disease, and other details. Assuming the child shows no signs of liver failure such as mental status changes or bruising mandating immediate attention, it would be prudent to consider obtaining initial laboratory studies to include CBC with differential and comprehensive metabolic panel.

Consultation with a pediatric subspecialist may be helpful at any time, but if the initial evaluation meets PUI criteria then referral to a tertiary pediatric center should be made.

It's a hot afternoon ahead in beautiful downtown Silver Spring. Maybe I'll look for a good sci-fi movie on the tube. (That last word really dates me!)

Hepatitis and COVID19 2

Bud WiedermannMay 15, 20222 Comments

If you are a worrywart* like me, now we have an outbreak to go with our pandemic to occupy our attention.

Why is it Taking So Long to Figure Out the Hepatitis Mystery?

Given the nature of the cases and symptoms, we should expect answers to take a while longer. Factors working against a quick answer:

The cause isn't one that is easily diagnosed with routine hepatitis testing, e.g. hepatitis A, B, C, D, or E. In fact, the case definition requires excluding these as a cause. If it were one of those, this would be relatively easy for epidemiologists.
Hepatitis of unknown etiology is not a reportable disease, meaning we don't have prior data to know how unusual the current situation is. It took some early clusters in the UK and Georgia (US) with severe outcomes to bring this to global attention.
Once a disease entity is identified as a concern, word goes out and then all kinds of reports flow in. This takes time to verify specifics and also makes it appear like everything is happening at once. Some of the reports are from older events, and it's even tougher to determine if they are connected to recent cases.
Adenovirus, a prime suspect, is a tough diagnostic entity. After infection, live virus can normally persist in the host for weeks to months, and the same is true for PCR testing. Thus, a positive test may not reflect recent infection.

Response globally and in the US is proceeding as one would hope for an outbreak investigation. Recently, the ECDC (European Centre for Disease Control) and the WHO joined forces to work on this. Individuals and organizations must apply for access to ECDC data, and I'm too lazy to do that. Instead, I look for my all-time favorite International Society for Infectious Diseases ProMED system to keep me current. Look at their first topic in the posting from last Friday and scroll down to the case numbers by country. Also, a little bit farther down are the adenovirus testing results. Now you get an idea of why this is so complicated and tedious.

CDC also is working hard on this, and I'd recommend all practitioners and any interested parents to look at their general overview. In particular, parents should note the signs and symptoms to look for in a child with hepatitis. Case definitions for reporting purposes vary slightly between Europe/WHO and CDC and likely will change as we learn more about this entity. Primary care providers should make liberal use of their pediatric GI and ID consultants for help. At Children's National we are working on clinical guidelines to assist both our internal as well as community providers.

A Few COVID Publications of Note

In my quick read through the Moderna vaccine results for 6-11 year-old children, it seems likely to be authorized by FDA for this age group. Of course, FDA has access to the raw data not provided in the article, so we do need to wait for their review. It's nice to have another option for this age group but of course we still want to see the data for children under 5 from both Pfizer and Moderna.

Two new reports appeared in JAMA this week, both related to vaccine effectiveness (VE) in children during the omicron period. One from CDC showed that VE for symptomatic infection in children and adolescents during the omicron period was modest but decreased fairly rapidly. For children 5-11 years of age, VE was 60% (95% confidence interval 55-65%) at 2 to 4 weeks post dose 2 and for adolescents also about 60% (44-71%). For the younger group 2 months after dose 2, VE dropped to 29% (24-33%). Adolescent data showed VE 17% (8-24%) at that time. However, data on adolescents who received a third (booster) dose showed at 2-6.5 weeks after booster VE was 71% (65-76%). That's more encouraging.

The second report was from New York state databases and looked at hospitalization rates for children 5-17 years of age. Although hospitalization rates were low in this group, it was very clear that completion of a primary vaccine series was significantly protective.

The accompanying editorial also was interesting. Vaccines clearly are important for children and adolescents. Now we just need to do a better job of getting this message across.

*Being the conscientious infectious diseases practitioner that I am, I was interested in the etiology of this particular wart. Apparently (I can't quite verify accurately) the term arose from a 1920s comic book series where the annoying protagonist caused others to worry.

Which Way is the Wind Blowing?

Bud WiedermannMay 8, 2022Leave a comment

My local weather hasn't been to my liking recently. I don't mind a little rain, but I want my May weather to be warm and sunny most of the time. I'd love it if SARS-CoV-2 would act a little sunnier too, but not sure this is the case.

The COVID-19 Winds

Hospitalizations in the US are clearly increasing, though not to the point yet that we could call this a true surge or wave. This is happening as we continue to see the BA.2.12.1 occupying a bigger piece of the pie across our country.

Looking ahead, however, we still need to keep our eyes on BA.4 and BA.5 subvariants, with South Africa being the main source of advance data along with wastewater monitoring worldwide. It's still a little early to see what's going on in South Africa, but some recent data suggests that these 2 subvariants have a great advantage in growth compared to prior variants and subvariants. A report from the UK has a nice assessment summary showing that the 2 new subvariants have a significant advantage in immune evasion that will be evidenced by increasing infection rates among both immunized and previously infected individuals as well as possibly changing effectiveness of monoclonal antibodies for therapy and prevention.

You can get a sense of how the research is moving from a preprint (non-peer reviewed) manuscript posted recently. It is laboratory modelling from structural analysis and pseudovirus neutralization assays, both helpful and relatively reliable in the past but could vary from what eventually happens in the real world. Again, time will tell.

Why Not Say It Clearly?

I stole this title from a book, apparently now out of print, that I read long ago to help improve my scientific manuscript writing. Not sure if it helped me, but maybe some of our friends at FDA and CDC should try to find a copy. A new article from Mayo Clinic reviewed COVID-19 vaccine explanations contained in FDA information fact sheets and from the CDC website. Short answer: it was too confusing for most of the US population to understand.

A target for such information is a 7th grade readability level that would apply to 83% of adults in the US. Utilizing validated tools they found that all documents pretty much failed; only the v-safe script achieved this grade level, and all failed on other measures. Given that we have extremely low acceptance of COVID-19 vaccines in the US, I hope that increasing attempts at effectively communicating risks and benefits will lead to better control of the virus.

I also recommend that healthcare providers at least skim this article to learn some tricks and tools for more effective communication with your patients and families.

The answer[s], my friend, [are] blowin' in the wind.

A Lot of Irons in the Fire

Bud WiedermannMay 1, 2022Leave a comment

This week I'm very challenged to limit the number of topics to discuss; much of interest, though nothing earth-shattering. I'll focus on 2 non-COVID items while slipping in a couple more ideas.

Speaking of COVID-19, it's mostly a good news situation for the moment. I continue to watch developments in the UK and it does seem like their uptick in cases is tailing off without having seen a big increase in hospitalizations. I hope we'll see that trend continue in the US. At the same time, I'm keeping a watch on South Africa. Gauteng province, the first alert to omicron problems originally, now is experiencing an increase in cases and hospitalizations likely driven by BA.4 and BA.5 omicron subvariants. It is also spilling over to other provinces. Time will tell if this is the next new surge there and worldwide.

Also, a good news/bad news package from the FDA. Counterfeit at-home COVID-19 diagnostic tests have appeared, but there are ways to identify them. Also, we saw a tentative schedule for FDA-VRBPAC meetings to discuss vaccines for the youngest children. Data submission from Moderna and Prizer is not yet complete, but I certainly hope one or both of the products will fulfill criteria for authorization.

Be Careful Counting Your Chickens

We now have the first detection of human influenza A H5N1 infection, a "bird flu," in the United States. Not a huge deal from a public health perspective in terms of numbers of people at risk. However, I'm glad it got a little news coverage because clinicians need to be aware of this. Birds have been affected in 30 states so far and include both poultry farms and backyard flocks.

The take-home message for front-line healthcare providers is to remember to inquire about history of close exposure to birds, not just chickens but wild birds as well, in anyone with influenza-like illness. CDC has guidance for what to do.

Fulminant Hepatitis Update

We've had some updates this week, but still more questions than answers. UK scientists have provided us with more information about their cluster investigation, as has the CDC for the cluster in Alabama. The association between adenovirus 41 (a gastrointestinal, not respiratory, adenovirus type) is still just that. The focus so far is on younger, previously healthy children. Whether the adenovirus is causal, a cofactor with another environmental or infectious agent, or just an epiphenomenon remains to be seen. In the meantime, probably a good idea for pediatric healthcare providers to discuss potential hepatitis cases with a subspecialist.

One final iron to mention: summer travel. Travel is opening up worldwide, increasing chance for spread of many infections. I take this opportunity to remind practitioners about measles, now increasing in several places around the world. It is still the most highly contagious respiratory infection known, though I'm waiting for one of the SARS-CoV-2 variants to exceed that. This high transmission rate combined with its rather prolonged incubation period and infectivity prior to clinical symptoms make it easy to take off in a community. Currently with general immunization rates relatively low due to the pandemic, many US communities are at very high risk if measles is introduced. Stay vigilant.

Month: May 2022