dengue – Page 2 – Pediatric Infection Connection

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.

Chocolate Bunnies

Bud WiedermannMarch 31, 2024March 31, 2024Leave a comment

It's Easter time, when my thoughts turn to chocolate bunnies. Not only do they taste better than real bunnies (well, to think of it, I may have never tested a real bunny), but I have been unable to find any reports of tularemia transmitted from chocolate bunnies.

Although we are clearly beyond the peak of winter respiratory infection season, we still have plenty to think about from last week.

Covid Household Transmission From Asymptomatic Children

A prospective study showed a high secondary attack rate (SAR) for covid in households likely stemming from asymptomatically infected children. The study was well designed to try to answer this question, identifying asymptomatic children in Canada and the US who were tested for SARS-CoV-2 for either non-household contact with a known covid case or as part of routine hospital screening. The study covered a 15-month period, and results were analyzed according to viral variants predominating in the community at those times: 1/31/21 - 6/30/21 was predominantly alpha or mixed variants, 7/121 - 12/19/21 was delta, and 12/21/21 - 4/22/22 was omicron. The authors compared household SAR of SARS-CoV-2 positive children to rates of those who tested negative. There are many nuances to the study, but here's the bottom line:

SARs were higher with younger index cases (< 5yo versus 13 - <18 yo), if the index case eventually developed covid symptoms (versus continuing asymptomatic), and during delta and omicron time periods versus the interval when alpha/other variants predominated. If you have access to the full text of the article, skim the Methods section to get an idea of the tremendous amount of effort involved in collecting this kind of data.

Dengue in Puerto Rico

This past week Puerto Rico health authorities declared a public health emergency due to dengue, the first time this has happened in the territory since 2012. What I'm sure is alarming to those authorities, beyond the sheer number of cases (524) in 2024 so far, is that this isn't peak dengue season. As befitting the mosquito vector, cases tend to rise in the summer when it is wetter. See below, with my apologies for lack of English translation. You can click on the Week 10 report in the PR DOH Arboviral Diseases Weekly Report for the full document.

In other words, the worst may be yet to come. (The dashed red line is the epidemic threshold which is higher in summer/early fall weeks; August usually is the peak month for rain in Puerto Rico.) We can certainly expect cases in the mainland US, including in non-travelers living in Florida and other states that have experienced autochthonous dengue cases in the past.

Meningococcal Group Y Alert

CDC issued another HAN report about increasing cases of invasive meningococcal disease due to group Y, a phenomenon that has been noticed for a couple years now.

Note that the incidence rate is very low; this represents a relatively small number of cases but still quite significant given the severity of meningococcal disease. Now is a good time for frontline healthcare providers to read up about meningococcal disease in general including indications for vaccination and identification of high risk groups, especially for this outbreak: age 30-60 years, Black or African-American descent, and living with HIV; as well as the usual risk factors of close contact with a case, people at the age extremes, certain immunodeficiency diseases such as complement deficiencies, and some college settings. The HAN notice includes many useful links.

How's Your Ventilation?

CDC issued revised guidelines for indoor ventilation to help prevent respiratory virus transmission, including SARS-CoV-2. Take a look and maybe ask your friendly office landlord how your building stacks up.

Apparently I've missed it for a couple years, but CDC also has an interactive tool to see how changes in ventilation may improve viral particle clearance. I disappeared down that rabbit hole playing with it for about half an hour. Note the disclaimer at the top of the web page about some information needing updates, though I think it mostly concerns the old 6-feet social distancing and other recommendations rather than the tool itself. Here are results from a home with intermittent HVAC operation, uncertain filter rating, and running the HVAC system for 1 hour after a 4-hour period of gathering. Better results can be achieved with continuous HVAC operation (i.e. keep it on continuously during times of high occupancy), high MERV-rated (Minimal Efficiency Reporting Value) filter, use of HEPA (High Efficiency Particulate Air) cleaner, and other factors.

However, before you overhaul your home system or threaten your office landlord, note what this is really saying. The outcomes pertain to effectiveness of particle reduction in the air, which is different from measuring whether it lessens transmission of SARS-CoV-2, influenza, RSV, or other viruses. It makes sense that there would be some correlation, but until someone does a more definitive study comparing systems and actual viral infection rates, we don't really know to what degree ventilation efficiency changes infectious disease outcomes. Compare this with the study of secondary household transmission mentioned at the top today's post - a more difficult study design with results more directly related to clinical outcomes than just a study of airborne particles in a laboratory chamber. And, parenthetically, the household transmission study did not include individual home ventilation as a factor, so even those results are incomplete. This is complicated!

Measles Update

Measles marches on in the US and across the world. US cases continue to grow, now at 97 since January 1, fed in large part recently by outbreaks in Chicago: 21 new cases in the past week just in Chicago alone. Here are the latest US numbers and distribution from CDC:

In Search of Easter Candy

Once again my wife and I have used our granddaughter as an excuse to buy Easter candy. She's a picky eater, now the only chocolate bunny she will touch must be dark chocolate without any added flavorings or other adulterations. I applaud her good taste, but perhaps next year I'll do this shopping more than a few days prior to Easter Sunday. I had no trouble finding a multitude of milk chocolate bunnies, some with various additives including peanut butter, salted and unsalted caramel, marshmallow, and other ingredients that I might have considered inedible if presented separately from chocolate. Plain dark chocolate bunnies apparently are almost extinct, definitely at least a critically endangered species.

I should have kept track of my steps and car odometer for this year's chocolate bunny safari, though I doubt even the thousands of steps I tallied will offset my Easter candy ingestion.

A Week of Autochthony

Bud WiedermannAugust 20, 2023August 20, 2023Leave a comment

Last week I was struggling to come up with enough new items to fill the post; this week I'm wrestling to pare down the list of topics. We've had some more concerning news about autochthonous tropical infectious diseases cropping up, but before I turn to that....

Is Covid Coming Out of the Doldrums?

Lots of headlines about this in the past week, some more hysterical than others. Staying alert, not panic, is the appropriate response.

First to wastewater. Looking at the past 6 months in Biobot, every US region is trending up, notwithstanding a slight drop in the purple midwest region.

Now look at the same graph spread out over a longer time:

So yes, we've had an upward blip recently, but nothing as dramatic as what accompanied serious clinical outbreaks in the past.

The other hype is about newer variants. Fortunately, we're still talking about omicron and primarily from the XBB subvariant group. I'll turn to the UK's nice graphs to highlight; results are similar but not identical to the US.

This Sankey diagram gives you an idea of the relatedness of strains:

The key question is how well the proposed autumn covid vaccine, derived from XBB.1.5, works against these newer variants. The answer is based mostly on conjecture at this time, we have no peer-reviewed hard data yet. The best guess is that it will not protect much against infection itself, nor will prior natural immunity. However, for the more important protection against severe disease, hospitalization, or death, it is likely to have an impact. Jennifer Abassi, a medical news reporter for JAMA, published a nice discussion. CDC and IDSA recently posted a brief explanation. Also in the news the past few days has been a newer variant, BA.2.86, now seen in a few countries sporadically including the US. It's much too early to know if this will become prominent.

CDC published updated data about monovalent and bivalent vaccination in the 6-month to 4- or 5-year-old age groups that showed good effectiveness in protection against urgent and emergency care visits. Also important to note is that these are relatively uncommon events in this age group, which is why you see different recommendations for vaccination in the US versus the UK for example. Going from the last section of Table 2 in the article, rates of these care visits from 12/24/22 to 6/17/23 were 4.4% in the unvaccinated group versus 0.9% in those who had received at least one bivalent vaccine dose. With a little arithmetic, the number needed to vaccinate at this level to prevent one additional ED/urgent care visit is about 30.

Reason to Avoid Proton Pump Inhibitors

French investigators published a cohort study linking use of PPIs in children to higher risk of serious infections. It included over 600,000 children receiving PPIs and a similar number as a control group not receiving PPIs, followed for a few years. The risks for serious infections as well as a number of categories of infection types were significantly increased. Most of the children had significant comorbidities. This association has been known in adults for a long while and is likely based on a variety of PPI effects including elevated gastric pH and alteration of the GI microbiome. That's not to say PPIs shouldn't be used in children, but there is a clear risk that should be explained to parents.

RSV Already in Florida

Florida is now seeing RSV infections in some jurisdictions. This isn't too surprising; Florida has a very different seasonal epidemiology than does most of the US:

It remains to be seen how RSV seasonality will stabilize in the post-pandemic/isolation era. A group in the Netherlands recently reported a switch to year-round transmission during the pandemic.

Along similar lines, a US study showed that ICU admissions for RSV consisted primarily of infants without risk factors; the study does have significant limitations. Findings may reflect the lack of partial RSV immunity conferred by prior RSV exposure of both mothers and infants.

It's still time to plan for use of monoclonal antibody and, if approved, maternal RSV vaccination. AAP and ACIP have a nice discussion available. Lots of logistical hurdles remain.

Autochthonous Malaria and Dengue

I posted about autochthonous malaria in Florida and Texas on July 2 and 9, and on autochthonous dengue fever in Arizona on 11/20/22. See the July 2 post for more about the definition of autochthonous infections.

Now we have a report of 11 autochthonous dengue cases in Florida. Closer to home, we've had a report of 1 case of autochthonous P. falciparum in a Maryland resident in the National Capital Area region. Falciparum malaria is significantly more dangerous than the vivax forms reported in Florida and Texas. Very little information was provided, but the letter does have links to good clinical information sites.

Autochthonous infections are tricky to diagnose given the lack of travel history to an endemic area. Climate change has expanded the geographic range of many insect vectors of disease. All clinicians should be aware of these diseases when evaluating febrile patients.

As a final note, my web wanderings about autochthony taught me something new about the term. Sadly, it has been used in a negative political (and racist) sense. An "autochthonous" flag protest disrupted a 2014 soccer match between Serbia and Albania.

Happy Thanksgiving, et al 2

Bud WiedermannNovember 20, 2022November 20, 20222 Comments

We're hosting a relatively small Thanksgiving gathering this week, but that doesn't mean I won't go crazy with planning and implementation. My goals are to have all of the food on the table, reasonably warm (except for the salads), within 2 hours of the intended sit-down time. A secondary goal is to keep the turkey off the floor during carving.

I suspect most of you are unaware, but this Thanksgiving day also marks the first anniversary of the initial report of the omicron variant appearance in South Africa.

Since I Mentioned Variants

Usually I give the weekly JAMA Medical News section only a cursory glance, but one item last week, written by Rita Rubin, was particularly well done. She effectively summarized a lot of evidence and viewpoints to paint a picture of what a covid winter wave might look like, and why. In addition to addressing the importance of immune-evasion properties of newer subvariants, she also sorts through some of the confusion about variant nomenclature and points out limitations of our standard pandemic tracking data like case numbers and hospitalization rates. It's become a difficult number to grasp now that much of home testing results go unreported, whether positive or negative, and large swaths of the US population have given up testing altogether. Wastewater monitoring probably is our most reliable, although imperfect, early warning indicator for a winter covid wave now.

Maricopa County - More Than Vote Counting

Maricopa County in Arizona features prominently in our news nowadays, mostly as a hotbed of election fraud rumors and innuendo. More significant (IMHO) is the report last week of an autochthonous dengue case (acquired locally rather than during travel to an endemic area). Dengue, a virus transmitted via mosquito bite, is endemic in many parts of the world, and virtually all cases in US residents are acquired via travel to these areas. However, climate change has greatly affected the range of the mosquito vector. Until now, Florida is the only US jurisdiction that has seen autochthonous dengue transmission.

2022 US Dengue cases in US residents as of 11/2/22, all travel-associated except for Florida.

Mosquitoes of the Aedes species (Aedes aegypti is also known as the tiger mosquito) transmit dengue, as well as Zika, chikungunya, and other viruses. Their range now extends across much of the US, including into the DC area.

More on Paxlovid Rebound

We now have an early glimpse via non-peer-reviewed preprint publication of an observational study of the rebound rates of covid positivity and illness following treatment with the oral antiviral agent paxlovid, compared to infection in individuals who did not take paxlovid. This preliminary report contains information on 127 participants who received paxlovid and 43 who did not. It covers the time period from August 4 to November 1, 2022, so all during omicron activity.

Rebound for positive virus testing (these were antigen tests) was 14.2% (18/127) in the paxlovid group versus 9.3% (4/43) in the no treatment group. For clinical symptoms rebound, the rates were 18.9% and 9.3% in paxlovid and no treatment groups, respectively. Another interesting nugget I noticed was that 20% of individuals in both groups still had positive antigen tests on day 10 after first positive test.

This is very preliminary information with a small number of participants, so the exact rates and differences between the 2 groups could change dramatically as more data are analyzed. The observational study design in general (rather than a blinded randomized controlled trial) also has limitations that could skew results.

Note that participants were all 18 years of age or older. Still, this is the start of getting a better ballpark assessment of covid rebound with and without antiviral treatment. For now, in the absence of specific pediatric studies, it remains prudent that covid-infected non-hospitalized children ages 12 years and older with weight at least 40 kg and with the appropriate risks and clinical status should be offered paxlovid treatment.

We Should Be Thankful

RSV, flu, and covid continue to cause a lot of angst in the pediatric medical community, and we know that some of the outcomes of the original Thanksgiving aren't worthy of celebration. But, let's remember to be thankful for the covid vaccines and treatments we do have available. We just need to do a better job of implementing these interventions.

Sunday's Washington Post Food section article on Thanksgiving holiday horrors triggered some post-traumatic stress. I wish I had known they were looking for stories, I would have submitted my greasy drippings jar/glass shards into the gravy pot fiasco from a while back, I'm sure it would have qualified for inclusion. It was a classic too-much-rushing-to-process-the-turkey-pan-drippings-before-the-turkey-turned-cold-drill. We didn't have any turkey gravy that year, but now I've switched to a recipe with roasted turkey wings that I prepare on Wednesday and probably tastes better than the original. So, remember to be thankful for silver linings, and have a safe and happy holiday!

Tag: dengue

Meh