dengue – Pediatric Infection Connection

Fall Back

Bud WiedermannNovember 3, 2024November 3, 2024Leave a comment

Once again I find myself, an ostensibly tech-savvy individual,* faced with manually resetting the time on 11 clocks and appliances in my house. Only my phone, laptops, and tablet appear to have joined the 21st century by self-correcting to eastern standard time. Of course, if our country had truly joined the 21st century, we wouldn't be making this twice yearly switch in the first place.

My election anxiety is somewhat mollified by focusing on infectious diseases, so you can categorize the following as therapeutic in nature.

WRIS

Still not much going on, though I was intrigued that my state of residence is 1 of only 2 to show up with moderate respiratory illness activity last week.

I'm pretty impressed by how quiet the SARS-CoV-2 front is. However, it's still around, and we can expect to see a resurgence sometime.

The fact that influenza has not yet appeared might indicate we are returning to a more "normal" flu season. The graph below shows how different the prior 3 flu seasons were from pre-pandemic experiences, where last year had a very early peak and 2020-21 and 2021-22 had very low and atypical peaks. (Apologies for CDC's labelling here, but if you stare at it long enough you can pick out which line goes with which year.)

New Development in Bird Flu

The so-called highly pathogenic avian flu H5N1 cropping up in dairy and poultry farms and in wild bird populations has been in the news for many months now. It still seems to be a mild illness in humans, most of whom have direct exposure to these farms. Only 41 humans have confirmed infections in 2024 so far. What's a bit noteworthy this week is that the virus may now have shown up in pigs. USDA officials reported probable swine cases at a backyard farm in Oregon where poultry, cows, and pigs all mingle. The farm itself has no role in commercial production of any foods, so it isn't a risk to others. What is of slight concern is the fact that pigs are involved. Pigs have a special place in influenza science because they have both human and avian flu receptors in their respiratory tracts, making the chance for a recombination event to occur if they happen to be infected with human and avian viruses at the same time. Most of the time this doesn't cause creation of a new pandemic strain, and I wouldn't hit the panic button at all now. Actually I'm surprised it took this long for swine infection to be found. The affected animals were all euthanized and multiple studies are ongoing, so I'm sure we'll hear more about this.

Polio

The news isn't great as both wild and vaccine-variant polio cases continue to be reported. This Global Polio Eradication Initiative map is a good summary.

No new cases have been reported in Gaza, with just the 1 case confirmed so far. The interrupted vaccination campaign in northern Gaza restarted this week.

Dengue Still Going Strong

I was browsing the CDC dengue page this week; infections are still plentiful.

Puerto Rico has the greatest number by far, but note that we have had autochthonous (locally acquired without travel to endemic areas) dengue in the mainland US (California with 11 cases, Florida with 49).

*

Can I really claim to be tech-savvy? I think so. I have an advanced degree in educational technology with classes that included instruction in networks and the various hardware involved; the fact that my schooling ended in 2008 shouldn't disqualify me. Also, this past week I restored to full health our K-cup brewing machine that became confused and wouldn't deliver the appropriate coffee volumes or allow the correct menu choices in its buttons. I guess in the interest of full disclosure, when I couldn't find a satisfactory replacement brewer online, my astute intervention was reading the instruction manual, realizing that I hadn't ever de-scaled the device in the approximately 90 years I've owned it, and made it new again using only a low-tech tool (vinegar).

In spite of my skills with technology and vinegar, I'll be performing my semiannual time resets for the foreseeable future; I could never part with my grandfather's clock.

Invasive Species

Bud WiedermannSeptember 15, 2024September 15, 2024Leave a comment

Last week I outsmarted myself. The closing photo in the September 8 blog I was sure would result in at least 1 person calling me out; I was then going to follow up in this week's post to explain about invasive species. I guess I forgot to factor in the politeness of my audience in not wanting to berate me for mistakes. (This is a more preferable explanation than the alternative that no one even read that post!)

Still not much going on with our summer respiratory season. The percentage of ED visits due to covid continues to fall nationally.

However, covid wastewater levels in the western US plateaued or even increased a little.

Measles Still Here

It looks like we have settled into a persistent trickle of cases in the US. I'm still holding my breath hoping we can avoid another major outbreak this year. The official tally for 2024 now is 251 cases from 30 states and DC.

Not included in the totals above is a new case occurring in an unvaccinated student at Western Kentucky University, probably acquired during international travel. It looks like that person attended several public events over a few days in late August; with an incubation period of around 2 weeks, we should be hearing soon if secondary cases resulted from this person.

Meanwhile, the UK has reported a measles death in a "young person who was known to have other medical conditions." With 2465 confirmed measles cases so far this year, the UK is much worse off than we are in the US. Still, it's unsettling to hear about measles deaths in high income countries. The UK has had 1-5 deaths per year since 2019 but hasn't had double-digit death figures since 1988. Best estimates are that, even with the best medical care, 1-3/1000 children with measles will die.

A Couple Vaccine Updates

Nothing really new here, but it's easy to overlook important guidance with the flood of emails and other reminders we receive. First is the official statement from ACIP about Hib vaccination for American Indian and Alaskan Native infants. It is the follow up from an ACIP meeting last June. For both socioeconomic and biologic reasons, it's been clear for decades that this population has a very high rate of Hib disease and also a less robust response to most Hib vaccines compared to the general US population. The best Hib vaccine for this group is a conjugate using the Hib polysaccharide PRP joined to an outer membrane protein from Neisseria meningitidis. The OMP is a carrier protein that helps infants form antibody to PRP, the real protective antibody here. This is the basis for all conjugate vaccines; it fools the infant immune system into thinking it is seeing a protein antigen rather than a polysaccharide antigen; PRP and other polysaccharide antigens are not well recognized by infant immune systems - normal infants even fail to form antibody to PRP with natural Hib disease. Conjugate vaccines fool infant immune systems.

At any rate, for a long while we've only had 1 Hib vaccine with the PRP-OMP combo: PedvaxHIB. This summer we saw FDA approval of Vaxelis, a hexavalent vaccine with DTaP, IPV, HepB, and Hib, the latter using the PRP-OMP product. Vaxelis is now officially recommended as an option for the AI/AN infant population, as well as for other infants. The recommendation for the AI/AN group was made on the basis of a phase IV randomized study of Vaxelis versus PedvaxHIB showing good antibody formation in both groups. No effectiveness study was performed because this population didn't have enough Hib disease present at a background rate to determine any significant differences with a new vaccine - PedvaxHIB has worked very well for these children in the past, another vaccine success and cause for celebration.

A second vaccine update is just the recommendation, again from CDC, for the next round of covid vaccines recommended for everyone 6 months of age and older. Again, nothing new, but it's a good resource to have all that information in one document. The tables serve as a quick reference for many different situations.

Mosquito Invasion

Any ID physician worth their salt will obtain an extensive travel history when seeing patients. We are mostly looking for clues to diseases seen mostly in international travelers, such as typhoid fever and the vector-borne infections that include dengue, chikungunya, malaria, and others. However, sometimes the travel history is negative but the patient ends up having one of those exotic diseases, acquired locally in the US (aka autochthonous infection). Such is the case recently with autochthonous dengue fever cases in Los Angeles County, CA. These cases appear when there is an existing reservoir of infected people plus a reservoir of the vector. For dengue virus, the vector is the Aedes mosquito, specifically A. albopictus and A. aegypti, plentiful in much of California.

The range of these mosquitoes have been increasing the past few decades at least, mostly due to warming of our climate. The last extensive study of Aedes presence in the US was in 2017, summarized by CDC.

As one of those people who seem to be particularly tasty for mosquitoes, I find it interesting (and depressing) that we have about 200 different species of mosquitoes in the US. I'm not terribly comforted by the fact that only about a dozen of these can transmit those infections we worry about. Besides the Aedes genus, we also need to worry about Anopheles and Culex mosquitoes.

Of these, it is Aedes that is the most versatile in transmitting disease to humans, implicated in Cache Valley virus disease, chikungunya, dengue, eastern equine encephalitis, La Crosse encephalitis, and zika infections. Anopholes can spread Cache Valley virus, and Culex are implicated in eastern equine encephalitis, St. Louis encephalitis, and Oropouche virus, though midges more commonly spread the Oropouche. Other viruses such as Jamestown Canyon virus can be spread by many different species of mosquitoes and vary with time of year and location.

As our global temperatures have warmed, the mosquito season has lengthened; in many locations mosquitoes are out and about throughout the year. Also, the idea that high altitudes are safer from mosquito-borne infections is becoming invalid in many parts of the world, including the US. It wasn't the altitude per se that mosquitoes didn't like, it was the cool weather which now is warming.

I realize that for many of you this is already too much mosquito information, but if you want more visit Arbonet.

More Invasion

Getting back to last week's post, I had mentioned that my wife was outside working hard to clear our back yard of poison ivy while I was indoors typing leisurely. It turned out she didn't find any poison ivy. The photo I placed at the end of the post wasn't poison ivy but rather a portion of the massive porcelain-berry plant she removed instead. While poison ivy is a native plant, not invasive but still hated, porcelain-berry is a horribly invasive vine deliberately introduced into the US for its attractiveness but quickly discovered to spread indiscriminately, eliminating native vegetation in its path. It is the plant world equivalent of pod people.

Seeing You in September

Bud WiedermannSeptember 1, 2024September 2, 2024Leave a comment

This month always bring me back to The Happenings version of "See You in September;" I remember it fondly from my junior high school era. The Harvest Month often is a transition period from summer to fall/winter infections.

The Respiratory Infection Front

Right on schedule, the ACIP published its official flu vaccine recommendations. Nothing new in there, but it's a good one-stop shopping place for seasonal flu information. Things remain calm on the overall respiratory illness view, and covid may have reached its peak.

However, I'm still waiting for covid wastewater trends to start heading down in most areas of the country (same link as above). We may not be out of the woods yet.

Also note that the covid vaccine from Novavax was authorized by FDA this week. I'll be interested to see how effectiveness compares to that of the mRNA vaccines; Novavax targets a slightly earlier variant (JN.1) than the Pfizer and Moderna products which used KP.2. KP.2 is decreasing in prevalence in the US but still is more closely related to the current variants KP.3.1.1, KP.2.3, KP.3, and LB.1.

We have more longterm follow-up information about myocarditis and covid, looking at both vaccine- and natural infection-associated complications compared to other ("conventional") etiologies. It looked specifically at individuals 12-49 years of age hospitalized with myocarditis. Without going into great detail, it was clear that vaccine-associated complications were less common than with myocarditis associated with conventional or SARS-CoV-2 infection; however, confidence intervals were wide for several of the outcomes due to low numbers of events.

I was excited to see a new update from the HIVE (Household Influenza Vaccine Evaluation) program that has been monitoring households in Michigan since 2010 and was expanded to cover other respiratory infections in later years. The new update covers the years 2015-2022. (The watermark in the figures below signifies this is an accepted manuscript that hasn't yet appeared in the print journal.) Even though it's limited to southeast Michigan, it is valuable data because it is an ongoing active surveillance program in these volunteer households and gives us a glimpse of how the pandemic affected other virus epidemiology.

Far Away Challenges

Mpox continues to rage in the DRC and other areas of Africa, with exported cases appearing in far-flung countries. In addition to vaccine, these countries need better front line diagnostic tests. WHO has requested test manufacturers to apply for emergency approval.

On the polio front in Gaza, we've all heard the good news that there will be a pause in fighting to allow for vaccine administration, but it remains to be seen if this will really happen. Regardless, this will be an extremely difficult undertaking, targeting over 600,000 unprotected children in the region.

Bugs Transmitting Bugs

Healthcare providers and the general public are understandably reeling from all the information about various outbreaks of vector-borne infections. It's important to keep in mind 2 main points: 1) Nothing is happening this year that hasn't happened before in the US. This is the season for vector-borne viral infections. 2) Global warming has increased both the range of these vectors, introducing these infections to areas that haven't seen them in past years, and also increased the season length that these infections circulate. We could see increases in all these infections in coming years.

Here's a breakdown of some of the viruses being hyped in the news.

West Nile Virus

Approximately 70-80% of infections are asymptomatic. The most feared complication, neuroinvasive disease, occurs in <1% of all infections but has a 10% mortality and higher rates of permanent neurologic sequelae such as paralysis. So far in 2024, we have had 289 cases from 33 states in the US, with 195 being neuroinvasive (reflecting the fact that only the worst cases get tested for WNV, not any change in asymptomatic rates). Here are some maps for prior years in the US:

As of now, nothing out of the ordinary for West Nile disease in the US. But, it's pretty common if you recognize that we're only identifying maybe 1% of infections.

Dengue

Here the risk is very high in Puerto Rico, but otherwise mostly restricted to travelers from the current epidemic/endemic areas. Some border states, especially Florida, are more likely to see autochthonous (locally acquired) cases. The asymptomatic infection rate is about 75%; 5% of the symptomatic infections progress to severe dengue with capillary leak syndrome and/or hemorrhagic complications. IMPORTANT CLINICAL PEARL: severe dengue usually appears when things otherwise look good - start of afebrile phase after 2-7 days of the febrile phase. This is the time to be very vigilant if dengue is suspected. The slide below (#42 in the pdf) is taken from a wonderful IDSA/CDC Clinician Call webinar this past week, available at https://www.idsociety.org/globalassets/idsa/multimedia/clinician-call-slides--qa/8-28-2024-clinician-call.pdf and https://www.idsociety.org/multimedia/clinician-calls/cdcidsa-clinician-call-update-on-dengue--other-vector-borne-diseases/.

Here are some numbers from the main CDC website above.

For 2024, the only locally acquired cases in the US have been in Puerto Rico (2676 cases), US Virgin Islands (85), and Florida (21), though those numbers are certain to rise since the season isn't over and reporting in general is delayed. If you add in the travel-associated cases, we've seen a little over 4000 in the US.

Oropouche Virus

This is a relatively mild illness for the most part. The asymptomatic infection rate is around 40%, but 4% of those with symptoms will develop neuroinvasive disease. Now there is concern for vertical transmission in pregnant people, still not completely clear. Management guidelines for infants with possible intrauterine infection are updated and available.

Although I was aware of Oropouche virus previously, this is the first year I've ever heard of the term "sloth fever" which only applies if you acquire the infection in the jungle. This is a slide from that same IDSA/CDC webinar, slide 69 in the pdf.

Oropouche may be over with in South America now, and the main risk area remaining is Cuba. CDC reported 21 US cases in travelers returning from Cuba.

Eastern Equine Encephalitis

Saving the worst for last. It's very uncommon, but you definitely don't want EEE. The encephalitis picture occurs in <5% of those infected with EEE virus, but of those with encephalitis the mortality rate is 30%, and 50% of survivors have permanent sequelae.

We've had 4 cases in 2024 so far. Here's data from prior years:

This is a horrible disease. Certainly precautions such as mosquito spraying and personal protection from bites should be implemented in areas where the virus has been identified.

Earworms

Not wanting to end on a depressing note from the rare but severe EEE disease, I thought of earworms. I'm not referring to the real earworm infecting corn ears, nor RFK Jr.'s brain worm, but rather the more contemporary use of the term. Last week I went down the rabbit hole for the Maurice Williams song "Stay," and this entire past week I've been unable to get it out of my head. Maybe I'll replace it with "See You in September."

Meh

Bud WiedermannJune 30, 2024June 30, 2024Leave a comment

I had expected last week's ACIP meeting to include more presentations and discussions about which covid strain to include in our fall vaccine. I viewed only a small portion of the meeting live (darn those pesky patient care issues!), so I probably missed any brief mention of strains; the slides themselves didn't address strain selection, other than to go with the FDA's statement for use of JN.1 lineage with preference for KP.2 if possible. I still found some interesting details about covid and nirsevimab and will share those with you. Perhaps meh is a bit of a harsh judgement, but I love the word.

In the meantime, thankfully still not much going on in the pediatric infectious diseases world this summer.

Love That New Technology

The CRISPR technology has been in the news for a long time. In case you had forgotten, like I did, it stands for Clustered Regularly Interspaced Short Palindromic Repeats and is now reported to have high sensitivity and specificity for detecting antiviral drug resistance and influenza subtype rapidly enough to be used as a point-of-need assay. The study itself requires journal subscription (thank you, GWU faculty status) to read in full. Investigators studied influenza isolates from the 2020-21 season looking primarily at AH1N1 and AH3N2 strains. The report is highly technical, beyond my ability to critique the laboratory methods, but the take-home message is important: if such a method is scalable (e.g. cheap enough) to employ across the world, including in resource-poor communities, it would be a boon to early warnings of resistant and/or new flu strains. I'm keeping my fingers crossed.

I must applaud scientists in this realm for their acronym constructions: in addition to CRISPR and others, they also used DETECTR (DNA endonuclease-targeted CRISPR trans reporter) and SHERLOCK (Specific High-sensitivity Enzymatic Reporter unLOCKing) assays. Elementary, my dear Watson. (And, that phrase never appeared in any of Arthur Conan Doyle's writings!)

Dengue HAN

Perfect timing after my mention of dengue last week, the CDC issued a Health Alert Network warning about dengue in the US. According to the Pan American Health Organization, early signs are that cases in the Americas this year will exceed last year's numbers, a year that was already much higher than previous years. Here's an example from the report of what's going on in the Caribbean subregion:

Puerto Rico is under a healthcare emergency because of dengue, and we will certainly have cases of autochthonous (acquired in the US without travel to an endemic area) transmission in the mainland US again this year, primarily in Florida and other southern states. The HAN is worth reading.

This would be a good time to review clinical presentations of dengue and be prepared to investigate/obtain consultation for suspected cases.

Pustules and Vesicles in Afebrile Infants <60 Days of Age

Pediatrics had a nice retrospective review of 183 infants from 6 academic hospital-based pediatric dermatology practices. It's open access and has a nice suggested management algorithm.

Note the first branch in the algorithm details key features to decide whether HSV evaluation and treatment is recommended.

ACIP Meeting Highlights

The regular meeting was spread over 3 days last week. Slides are posted, and I picked out a few that contained interesting new information.

First, even with all the problems of supply chain and late administration, nirsevimab appears to have been incredibly effective in preventing RSV hospitalizations and healthcare visits.

Yes, that's about 98% effectiveness in preventing hospitalization, with very narrow confidence intervals. When this slide was shown it elicited a round of applause from the committee members. This is truly remarkable. Similar results were seen using a different RSV surveillance method. Both the above and below slides are from the Payne presentation on June 28.

It appears we'll have better availability of nirsevimab for the next RSV season, so please prepare for that. I find myself fantasizing of some future day when new pediatric trainees won't see hordes of infants hospitalized with RSV bronchiolitis, with worried parents at the bedside.

Second, although I mentioned I didn't see any new data/discussion about strain selection, the covid vaccine discussion had useful updates about epidemiology and risk factors, mainly from the Haver presentation on June 27.

About half of children hospitalized for covid had no underlying risk factors; we already knew that, but here's a more detailed breakdown. Note that these numbers are for the past year, at time when virtually all US children had some prior antibody from infection and/or vaccine.

Here is the vaccination status, including the low numbers who received the 2023-24 version, of the hospitalized children:

One BIG disappointment for me with the presentations: there was no mention of a control group - i.e. what are the rates of underlying medical conditions and 2023-24 vaccine status in the pediatric population as a whole? Adjusting for rates in the general population would provide a better estimate of the relative contributions of risk factors and vaccination to more serious outcomes and give us a better handle on the magnitude of benefit of vaccination, for example. Still, nothing has changed; for the individual child, covid vaccination is better than not being vaccinated, even factoring in the low rates of serious outcomes and adverse vaccine events in children.

The 2023-24 vaccine was highly effective against emergency department and urgent care visits in all age groups, though waning of protection over time was seen. Lack of enough events of hospitalized children precluded reliable estimates of VE against pediatric hospitalizations. (Link-Gelles presentation June 27.)

Bird Flu

Exciting (to me) news that CDC is collaborating with the Michigan health officials to carry out a seroprevalence study for H5N1 infection in Michigan dairy workers. This should produce much better information about asymptomatic and mild infection in humans and possibly lead to more clues about transmission.

Covid Uptick?

Still a question, but positive test percentages are increasing, albeit at a low level and predominantly driven by western states.

Wastewater variant detection is lacking across the country, see all the block dots (no sequencing data) below, but you can magnify your area of the country and find a few sites with enough data to determine predominant covid strain.

For example, in my neck of the woods most of the sites have no sequencing data. Of the 2 that did, one showed a predominance of KP.2 and the other LB.1. Nationally, KP.3 is starting to exceed KP.2. Again, we're still at low numbers.

A Tip of the Hat to "The Simpsons."

I knew that "meh" might have been adopted from a Yiddish term meaning so-so or unimpressive, but it looks like a 1994 episode of the TV series The Simpsons, featuring ultraconservative Sideshow Bob, popularized the term. Lisa Simpson was investigating voter fraud as the reason Sideshow Bob was elected as Springfield's mayor, and the "meh" word was uttered by a Hall of Records bureaucrat when Lisa expressed disbelief that he would give her the entire mayoral voting records that should have been kept secret. (Thie episode is available only with subscription, but I verified the quote at about 15:30 time in the recording.)

Voter fraud 30 years ago?

The Birds

Bud WiedermannApril 7, 2024April 7, 2024Leave a comment

Bird flu has been in the headlines, accompanied by the usual extremes of concern levels. The past few weeks reminded me of Alfred Hitchcock's 1963 movie "The Birds," especially a diner scene where an elderly (my age?) amateur ornithologist (Ethel Griffies as Mrs. Bundy) attempts to explain why the "brain pan" size of a crow or blackbird makes any organized attack on humans impossible. The discussion is interrupted by another customer declaring the end of the world, interspersed with background shouts of orders for blood marys and fried chicken with baked potatoes.

Before we get to bird, a few other items of note.

Dengue Update

Maybe things aren't quite as bad, with a downward trend now apparent in the Americas.

The bulk of this atypical seasonality increase is from the Andean and Southern Cone regions of South America. Brazil by far leads the way, and Argentina, Peru, and Paraguay are in a second tier by numbers of cases. Here's a numbers breakdown for last week and for the calendar year as a whole:

Don't Dismiss Covid

Yes, the current variants and immunity levels in the US seem to result mostly in mild disease and numbers continue to trend downward, but we are seeing well over a thousand deaths per month from covid in the US. It is still a devastating disease.

Measles Still Hanging Around

No outbreaks in new jurisdictions in the US in the past week; Illinois and Florida still account for most of the cases this calendar year.

Highly Pathogenic Avian Influenza (HPAI)

The name itself is pretty ominous, cue those eery bird sounds from the movie. The biggest event last week was the confirmation of a case of influenza A H5N1 infection in a man from Texas, almost certainly acquired from the dairy cows he worked with. He was treated with oseltamivir and apparently is doing well. CDC issued a health advisory through their Health Alert Network last week, including a lot of good advice and helpful links. People who are around birds or dairy animals should take care; this includes those with backyard chicken flocks. The public health messaging has been pretty consistent: no cause for alarm, and certainly no reason to avoid dairy products or eggs at your local store (assuming the dairy products are pasteurized). FDA has a great Q&A page on this.

Note however that we have pockets of these viruses throughout the US, including in wild mammals.

We can be reassured that all of these strains are being tracked and sequenced worldwide through the Global Influenza Surveillance & Response System (GSAID). Scroll down at that link to watch an animation of the geographic spread of influenza A H5Nx viruses worldwide over the past few decades.

We have several antiviral therapies available, and vaccine prototypes are ready to enter mass production if necessary. So far, none of these strains seem well adapted for human-to-human spread, but if that happened it would be a major event that would cause much more concern. I'm also watching to see if this appears in pig populations, since swine flu viruses have been seen in the past to foreshadow human spread. Pigs have similar flu viral receptors to humans, so spread in pigs can be seen prior to a jump to humans. Thankfully, many of the events that facilitate spread among different animal species also are associated with lower virulence, so clinical impact is minimal.

Don't Look Up (Without Your Eclipse Glasses)

Yes, I know it's yet another movie. Just be careful with tomorrow's eclipse.

Tag: dengue