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.
Those pandemic doldrums may be lifting, but it's difficult to determine in today's post-pandemic era of reduced reporting. First, a look at a couple other things from a slow week in the world of infections.
ProMED Still Going Strong
I mentioned last week that my most cherished web site, ProMED, had some internal turmoil that threatened its existence. I don't know if the disagreements have been solved, but their postings have continued. Here's an example from last night's email of topics:
ProMED Digest, Vol 107, Issue 221
1. PRO/AH/EDR> Anthrax - Indonesia (07): (JT) cattle 2. PRO/AH/EDR> Crimean-Congo hem. fever - Asia (22): Afghanistan 3. PRO/EDR> Pertussis update (21): USA (NY) 4. PRO/AH/EDR> Canine influenza - North America (08): USA (OK) RFI 5. PRO/AH/EDR> Listeriosis - Americas (05): (USA) kosher ice cream, recall 6. PRO/EDR> Leishmaniasis, Americas (10): Brazil (MG) 7. PRO/AH/EDR> Leptospirosis - Italy: (VN) swimming, river 8. PRO/EDR> Measles update (36): Sweden, cruise ship 9. PRO/EDR> Meningitis, meningococcal - Norway: (VF) fatal, ex Greece 10. PRO/AH/EDR> Newcastle disease - Poland (02): (PD) poultry, spread 11. PRO/AH/EDR> Anthrax - USA (07): (ND) cattle 12. PRO/AH/EDR> Lumpy skin disease - Asia (11): Indonesia ex Australia, cattle, disputed, RFI 13. PRO/EDR> Measles update (37): South Sudan (WH) fatal, children 14. PRO/AH/EDR> Avian influenza (129): Americas (Argentina) sea lion, HPAI H5 15. PRO/AH/EDR> Echarate virus - Peru: (JU) new variant 16. PRO/AH/EDR> Eastern equine encephalitis - North America (05): USA (NC) 17. PRO/AH/EDR> Brucellosis - Paraguay (01): (AS) veterinary school, RFI 18. PRO/AH/EDR> Crimean-Congo hem. fever - Asia (23): Iraq 19. PRO/AH/EDR> West Nile virus (12): USA (NM, DE) 20. PRO/EDR> Pertussis update (22): Canada (SK)
It's a longer list than most of their posts. I couldn't remember what the Echarate virus (ECHV)was, so I looked deeper at that one. Turns out ECHV is a Phlebovirus, a genus of viruses that can cause nonspecific febrile illnesses in humans. It is transmitted primarily by sandflies, mosquitoes, and ticks. Echarate is the capital city of the Echarate District in Peru. One of the many reasons to use insect repellant.
Vaccination of Pregnant Persons
The timing worked out well for me, so I tuned in to a CDC COCA call on vaccination during pregnancy. The event recording and slides are available at their website. Virtually none of my patients have been pregnant people, but as with most pediatric healthcare providers it's been very common for parents of my patients to be pregnant at the time of their child's visit with me. So, pediatric providers have a role in encouraging vaccination for pregnant people.
No surprise, but uptake of the 3 vaccines with specific benefits during pregnancy (Tdap, influenza, covid) has been pretty poor lately:
The benefits of influenza and covid vaccines accrue to both the pregnant people, since those diseases are more severe during pregnancy, as well as to providing antibody to their newborns. Tdap vaccination is recommended for every pregnancy, regardless of prior immunization status, because pertussis protection wanes quickly over the year following vaccination and therefore is unlikely to provide newborn protection for a subsequent pregnancy. Tdap immunization specifically for pregnant people was first recommended in 2011 but excluded those who had prior Tdap vaccination; that was amended in 2012 to include all pregnant people regardless of prior vaccination.
Multiple studies have shown the effectiveness of this approach, seen above in the reduced rates in the less than 1 year-old group. Of course, the further sharp decline in recent years is related to pandemic isolation when rates dropped for multiple infectious diseases. We likely will see increases back to pre-pandemic levels or higher as we return to more normal societal interactions, so vaccination for all 3 conditions will become even more important.
At the time of this writing, we're still waiting on the FDA to make some sort of determination on RSV vaccination for pregnant people to protect their newborns, although the need for this intervention is attenuated by the recent approval and recommendations for nirsevimab, the long-acting anti-RSV monoclonal antibody for newborns.
Recommendations for how to guide pregnant people in their vaccine choices begins on slide 38 of the presentation, found at the link mentioned above.
'Demic Doldrums
At least one indicator suggests a significant change that could mean the summer calm of low covid rates is lifting. Still it's difficult to determine since almost all reporting has reduced. Even hospital reporting has changed post-pandemic, so case rates for hospitalizations and ED visits are less reliable. You can still see the upward trends, though still very low rates overall.
More significant, however, are new wastewater reports particularly in the upper Midwest. I've detailed previously that wastewater monitoring in the US is voluntary and very sketchy, but trends in this one region now approach last winter's numbers.
Again, time will tell whether this summer breeze ends our covid doldrums.
I think we've seen a bit too much hype about covid variants lately, specifically with the EG.5 (a descendent of XBB.1.9.2) that has appeared in both lay press and medical updates. Remember that overall this is based on relatively few viral samples tested and is very hard to predict for the future. Also, no hint yet that it produces more severe disease, it just has a growth advantage and effective immune escape properties compared to prior prominent variants.
Most important is that virtually everything going on now is in the XBB lineage which is included in the planned autumn covid vaccine dose. It should provide good protection against all of these.
A Tune Stuck in My Head
Speaking of summer breeze, given my age I immediately thought of the Seals and Crofts song of the same name listed as #20 in Rolling Stone's best summer songs. I hadn't realized it was also a hit for the Isley Brothers a couple years later.
Seems like Shark Week has been everywhere the past few days. I can't recall ever watching anything on the Discovery Channel's Shark Week offerings, but I was very aware of it because I live a 20-minute walk from their (now former) corporate headquarters in Silver Spring, MD. Every year around Shark Week they transformed their several story building into a shark.
Perhaps this all influenced me to provide you with an in-depth look at how I approach evaluating an article that might change medical practice. It's a routine I've refined over several years and taught in my prior EBM classes as well as in other settings.
A Deep (Nose)dive
In early June I saw the advance publication of a randomized controlled trial of antibiotic versus placebo for acute bacterial sinusitis. I made the conscious decision at that time not to mention it in this blog because I decided it did not have direct applicability to clinical practice. I might also have been swayed by the fact that I wanted to mention my new washing machine in that blog, and, well, some things just gotta make room for the important stuff.
However, the article appeared in last week's JAMA and was accompanied by an editorial in JAMA as well as an editorial in JAMA Otolaryngology, plus appeared in several medical feeds. Given all the hoopla, I acknowledge I made a mistake in early June and should revisit the article, this time in depth. I'll lead you through the process and my conclusions.
Step 1 - Is it worth my time to evaluate an article in depth?
This step only takes a minute, usually from reading the title and the abstract. If it sounds intriguing and has a study design likely to yield accurate results (e.g. a double-blinded randomized controlled trial for therapeutic interventions) I keep going.
This report is a randomized controlled trial aiming to determine "if antibiotic therapy [for acute bacterial sinusitis] could be appropriately withheld in prespecified subgroups." The abstract sounded interesting with a good study design, so on to the next step.
Step 2 - Immediately go to the Methods section; do not read the Introduction, Results, or Discussion sections.
Whenever I think about this step I'm reminded of the sea (intentional shark pun) of horrified faces in my student/trainee audiences when they first hear this. There's nothing more mundane than the Methods section of a scientific article, but if the methods aren't sound I don't waste my time reading the rest of the paper.
This was a study taking place over 6 years, extended due to pandemic interference with enrollment, at 6 different study sites. In a multi-center study, especially one interrupted by a pandemic, there is a risk that lower-enrolling centers will make mistakes in following the protocol that could cause loss of subjects or missing data. Looking at the enrollment and follow-up diagram, fortunately this did not appear to be a big problem for this study. Also, looking at their Table 1, most of the subjects were enrolled at just 2 centers: Children's Hospital of Pittsburgh (about 3/4 of enrollees) and Kentucky Pediatric and Adult Research (about 15%). The latter organization is a for-profit company, a feature that always raises my eyebrows with medical research, but they've been in business in rural Kentucky since the 1980s, and I don't have any particular concerns about them.
Eligible subjects were children ages 2-11 years who fulfilled criteria for persistent or worsening acute sinusitis in the AAP's 2013 clinical practice guideline. They also needed to have an initial score of at least 9 on the validated Pediatric Rhinosinusitis Symptom Scale (PRSS) which was used as the primary means of evaluating treatment results. Here's a quick look at the scale from the article's online supplemental information.
Points are assigned as 0 for No, then 1-5 from Almost None to An Extreme Amount. As you can see, the minimum score of 9 to be eligible for the study can be achieved with fairly mild symptoms. More on that later.
I won't mention this in depth, but I felt the exclusion criteria were reasonable. In particular, those with more severe symptoms such as temperature > 39 C for 3 or more consecutive days were excluded.
The enrolled children were stratified according to whether parents reported presence or absence of colored nasal discharge and then randomized randomly to receive amoxillin/clavulanate 90 mg/kg/day/6.4 mg/kg/day or placebo divided in 2 doses for 10 days, in a double-blinded fashion. Anticipating later problems with side effects that did occur, the authors mention that they chose amoxicillin/clavulanate over amoxicillin alone to provide broader coverage for all pathogens, presumably those producing beta-lactamase. So, I did note this wasn't quite a real-world situation where amoxicillin might be a better choice based on less GI side effects. Children had nasopharyngeal swabs for Streptoocccus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis obtained at enrollment, and outcomes were compared based on these results.
I immediately wondered about the placebo which was said to be "matching." Most pediatric healthcare providers, as well as parents of young children, know that it is pretty easy to determine if a child is receiving an antibiotic containing amoxicillin due to the odor of the medication and also sometimes urine odor. I wanted to find out if the placebo was truly a good match for the study drug, but the article itself had no further details. Fortunately, the online supplemental materials included the 73-page study protocol. On page 31 beginning on line 790, the placebo is well-described and included reassurance that it was identical in appearance, odor, and texture to the amox/clav.
I'll spare you the statistical details; although I'm not a statistician, I didn't notice anything nonstandard in the analytic methods.
Step 3 - Results
Finally we get to some of the meat of the article! In total, 254 children were evaluable in the treatment group and 256 in the placebo group. Almost 2/3 of enrollees were 2-5 years of age, so a bit skewed towards the younger part of the age range. I was interested in the PRSS scores of those evaluated. In general there was good distribution along the PRSS range, and the 2 treatment groups were similar:
Now, what about the outcomes. The investigators predetermined that a difference in PRSS scores of 1.0 was clinically meaningful. I would question this, given that it doesn't take much to drop a point from a PRSS score - just rating stuffy nose as dropping from "a little" to "almost none" would do it. Here is what was seen for the group as a whole:
Here's what was found when broken down by culture results:
I did notice in all the analyses that children experienced the biggest 1-day drop in PRSS scores in that first day, regardless of treatment group. This represents either natural history or perhaps a placebo effect of just being enrolled in the study and parents being required to pay close attention to their child's symptoms.
With further analysis, it turned out that children with cultures showing pneumococcus or Hi showed statistically significant improvement with antibiotic compared to placebo. Presence of Moraxella, absence of any pathogens in culture, and snot color had no predictive value of response. So, the implication is that culture showing pneumococcus or Hi in culture, along with the clinical AAP guidelines, could be used to further narrow the number of children receiving antibiotic treatment unnecessarily.
In terms of the down side, the main problem was clinically significant diarrhea seen in 11% of the antibiotic group and 5% of the placebo group. If amoxicillin had been used the rate in the antibiotic group likely would have been much lower.
Step 4 - Now read the rest of the article
I look particularly at the Discussion section to see how the authors propose using the results and also how they describe limitations of their study. They describe their study findings as being used in 1 of 4 ways:
Treat everyone fulfilling AAP guidelines, no testing for pathogens
Start presumptive treatment for everyone fulfilling AAP guidelines, test for pathogens, and stop treatment if no pneumococcus or Hi found
Test for pathogens, wait for results, and treat those who have positive pathogen test
Watchful waiting for everyone
All of those options seem possible to me, given that diagnosis is so difficult and the vast majority of these children do fine as long as they are followed closely. Multiple practical problems arise with options 2 and 3 because they require sending a culture and presumably making a special request to the lab to look for and report presence of any pneumococcus or Hi. Depending on the office practice, this takes time and has additional problems/delays if a weekend or holiday is involved, plus making sure the patient isn't lost to follow up. If your practice is situated in a hospital like Children's Hospital of Pittsburgh this might be more feasible than if this is a practice site that sends cultures to a commercial lab.
The authors listed 5 study limitations, some of which seemed trivial to me. First, their original target sample size wasn't reached due to the pandemic. However, their results still reached statistical significance, so this isn't a real limitation. Second, changes in gut microbiome weren't examined. As we find out more about how the microbiome interacts with other aspects of health, it becomes even more important to limit unnecessary antibiotic use. Third, as stated previously children with certain severe symptoms were excluded use of cultures in that setting can't be assessed. Similarly, the fourth limitation was that children not meeting study entry criteria, or even those with parent characteristics less likely to enroll in research studies, might have introduced bias. This is true of all prospective clinical trials so hardly needs to be mentioned here. The fifth and final limitation mentioned was that the gold standard for diagnosis of bacterial sinusitis, quantitative culture of a sinus aspirate, wasn't used. This would have been ideal, but it would be extremely difficult to enroll a child with a relatively minor illness if they would be required to undergo an invasive procedure with little direct benefit to the child.
The main study limitation I appreciated is that the differences in PRSS scores between antibiotic and placebo groups weren't terribly large, an average of 1.69 points. I wonder whether parents would find this an important difference, particularly since after a couple days we are talking about the milder end of the scoring system. There isn't enough detail provided, even in the supplemental data, to know how many individual patients experienced a decrease in symptoms that might be important to parents.
Step 5 - Is there evidence of bias in the study?
The study was funded by NIAID, probably the cleanest funding source there is in terms of bias. I did note that a couple of the authors disclosed financial arrangements with a company called Kaizen Bioscience. I had to research the company a little, it is a small for-profit pharmaceutical company. One of the arrangements involved a proprietary formulation of amoxicillin/clavulanate, so this is a very real potential conflict of interest with the study. On the other hand, I am acquainted with a few of the study's authors, and I don't for a minute suspect they would purposely alter their report based on this connection. The problem, however, is really with implicit bias, the bias we all have but aren't aware of. Did the authors subconsciously "spin" their report to appear more favorable? I don't view this article any differently based on the potential for implicit bias, it's just something to keep in mind particularly if future studies show different results.
After all of this, how do I put everything together?
I wish I had been keeping track of time, but I estimate it took me at least 3 hours of working through the article, not counting time thinking about it while in the shower or writing this post. Ultimately I came back to my original thought - this study isn't ready for adoption into clinical practice.
But, after picking through this with a very fine-(shark)tooth comb, this study's design and reporting are almost impeccable, really a model for others who are beginning clinical treatment research careers.
In the interests of not boring you completely, I left out a lot of other details in the study (see metatranscriptomics for example). Read the article if you have more interest in pediatric sinusitis.
'Demic Doldrums
We continue to see some uptrending in SARS-CoV-2 in wastewater, but still at low levels, according to Biobot.
Similarly, CDC reports slight upticks in covid hospitalizations and ED visits.
Dr. Rivers at Force of Infection notes that the current upticks resemble what we saw in the summer of 2021, just before the delta wave. I think it's a little early to be saying that, plus so far nothing as virulent as the delta variant is prominent. I wouldn't be surprised by at least a mini-wave this fall.
Shark Week
I decided to explore more about Shark Week; one of my (surfer) brothers-in-law did survive a shark attack many years ago, requiring several surgical procedures. I was sorry to learn that the Shark Week shows have become a form of docufiction, whereby true documentary filming is overlaid with fictional information or staged events to increase viewers or readers. In our current age of fake news and artificial intelligence doctoring of reality, we don't need this.
I'm a longtime Johnny Cash fan, and the weather reminds me of his cover of the song Jackson with his wife June Carter Cash. Things are heating up in the country and world-wide now. We'll certainly see all kinds of health effects from this, including but not limited to infectious diseases. For now, try to keep cool, hydrated, and apply plenty of sun screen.
Also Remember Mosquito Protection
Speaking of climate change, the Florida Department of Health reported 2 more cases of autochthonous malaria in Sarasota County (see below), bringing the total to 6 cases in that region. Now is the time to take extra precautions for mosquitoes for residents of and travelers to that area.
By David Benbennick - The maps use data from nationalatlas.gov, specifically countyp020.tar.gz on the Raw Data Download page. The maps also use state outline data from statesp020.tar.gz. The Florida maps use hydrogm020.tar.gz to display Lake Okeechobee., Public Domain, https://commons.wikimedia.org/w/index.php?curid=570156.
CDC Budget Cuts
I can't find any official announcement on the CDC website, but Kaiser Family Foundation and various media entities have reported seeing emails from CDC to state health departments detailing some of the effects of the recent Biden administration budget cuts. Specifically, funding for sexually transmitted infection and pediatric vaccine support are being cut significantly. This couldn't come at a worse time. The impact will be most severe on those populations already at high risk such as rural populations and others lacking medical insurance coverage and access to healthcare. Here's hoping the feds find a workaround for these cuts.
'Demic Doldrums
We continue in a covid lull worldwide, with only a few areas showing increasing activity according to WHO.
On the variant front, not a lot to report although a new omicron subvariant, XBB.1.5.26.1 abbreviated as EU.1, may be the latest to watch. It's still at very low numbers in the US but has a significant growth advantage over other circulating variants. Remember that XBB.1.5 is the variant included in the upcoming covid vaccine for this fall.
I don't strictly fulfill diagnostic criteria for entomophobia, but my long-suffering wife would disagree when it comes to my fear of mosquitoes. I believe it dates back to a camping trip to Big Bend National Park when I was maybe 7 or 8 years old. I woke up to about 100 bites on my body, while my best friend in the same tent had about 2. It was then that I realized I was very popular with mosquitoes; I'm a mosquito magnet.
I'm particularly reminded of this with the current malaria transmission in Florida and Texas. One of my earliest childhood memories is of my father intermittently taking to his bed with high fevers and shaking chills, a vigorous man reduced almost to an invalid for a few days. He knew this was his malaria relapsing, related to his World War II service in North Africa. He had either Plasmodium ovale or Plasmodian vivax, the 2 types of malaria that have an exoerythocytic phase that requires primaquine treatment to eradicate, after initial treatment with choroquine or other agent. Apparently he didn't have access to primaquine, although it was discovered in 1946 and approved for use in the US in 1952, before I was born. Either he ultimately did get treatment or the episodes just burned out by themselves, but he didn't suffer from relapses in later life. Even though these forms of malaria aren't as deadly as P. falciparum, morbidity is still significant.
So, make my summer cocktail sunscreen, plenty of water, and DEET. (Not to be confused with prior advice of some extremists for covid treatment, the sunscreen and DEET are topical agents, only the water is to be ingested!)
Ever read Beowulf? Me neither. Nor do I plan to ever read this epic poem consisting of 3182 lines of alliterative verse. Recently I did read Grendel by John Gardner. Grendel is the monster who was killed by Beowulf in the famous poem. Gardner's book is told entirely from Grendel's perspective, very different from how Beowulf and the other humans saw things of course.
Malaria Season
Practicing in the Washington, DC, area for almost 40 years meant that I had a steady diet of malaria. Our "malaria season" was towards the end of summer when vacationing families returned home after visiting relatives in malaria-endemic countries. This seasonality abated a bit during the pandemic when international travel was scarce, then came back with a vengeance. Now, however, autochthonous malaria has been reported in Florida and Texas.
Autochthonous, from the Greek autokhthon meaning "sprung from the land itself," in this instance refers to malaria acquired without visiting a malaria-endemic country. I didn't mention the initial CDC report a couple weeks ago, but now that a second state is involved and CDC issued a health alert advisory, I'll attempt to summarize what's happening.
We still have virtually no clinical details about any of the 5 cases, but CDC implied they are all due to Plasmodium vivax which is not as severe/deadly as P. falciparum. Autochthonous malaria in the US was common in the old days, but since effective mosquito control programs in the 1950s it has been scarce. Prior to the current reports, we hadn't seen autochthonous malaria since 2003. High risk areas in the US are those that have high population density, plenty of Anopheles mosquitoes (including favorable conditions for their reproduction), and a source of people who have recently traveled from malaria-endemic areas. So, it's not surprising that Florida and Texas are points of origin now.
Speaking of mosquitoes, climate change has greatly increased the range of various insect vectors of disease; for example, Lyme disease risk has expanded geographically in recent years as deer ticks broaden their range. Anopheles mosquitoes are present in virtually the entire US.
For frontline providers, malaria shouldn't be the first thing to suspect in a child with fever in the US, but recognize that in cases of prolonged fever it is a consideration even without a history of international travel. Look at the CDC's malaria website for more details, and read this article if you want to see a longer discussion of (prepandemic) autochthonous malaria.
Foodborne Disease is Back
Another sign that the pandemic is lifting is this CDC report of 2022 data. Certain foodborne illnesses such as Shiga toxin-producing Escherichia coli, Yersinia, Vibrio, and Cyclospora infections increased compared to 2016–2018 data; Campylobacter, Salmonella, Shigella, and Listeria incidences didn't change much. Although they didn't show the data in this report, foodborne diseases decreased in the 2020-2021 time period.
I was a bit disappointed that, although the report did mention increased use of culture-independent diagnostic testing rather than culture, it did not mention the fact that the highly sensitive CIDT methods can be more prone to false positives. This makes it difficult to compare trends across time periods.
Ideally one would perform a backup culture test for bacterial pathogens particularly to detect antimicrobial resistance; CIDT can not test for this.
Can We Shorten Treatment Duration for Pediatric Urinary Tract Infection?
The short answer is yes, but the more difficult question is how to decide which patients are appropriate for shortened therapy. Even this randomized controlled trial couldn't answer that question. The study compared 5 versus 10 days of therapy for UTI in children 2 months to 10 years of age. Children who showed clinical improvement at 5 days treatment were then randomized to another 5 days of antibiotic versus placebo. Failure rate in the 10-day treatment group was 0.6% versus 4.2% in the 5-day group.
Ultimately I think the details of study design doomed this trial to leave this question mostly unanswered. In particular the duration of followup after stopping antibiotic was too short for the 10-day group (which would have skewed results to a falsely low failure rate). Fundamentally the problem with UTI treatment in children is trying to determine which children have pyelonephritis versus just cystitis, much more difficult in children than in adults. Pyelonephritis likely requires more than 5 days of treatment.
This study definitely adds to our understanding of pediatric UTI but I don't think is immediately transferrable to clinical practice. The accompanying editorial offers some ideas in this regard.
'Demic Doldrums
We continue to enjoy relief from covid from the standpoint of no evidence of major surges around the world, just continued pockets of upswings in disease activity (tempered by the knowledge that we aren't tracking it very well now). Of course, the number of total cases in this WHO graph, as of June 28, is pretty depressing overall.
According to WHO, confirmed covid deaths now number 6,947,192.
Blood Group and Covid
I have blood group A positive. Should I be worried? It's been known for a while that individuals with type A blood have a slightly higher risk of SARS-CoV-2 infection, and this recent article lends some credence to these observations by supplying a biologic explanation. The A blood group antigen is very attractive to the receptor binding domain of the virus, including omicron variants. But no, I'm not concerned. The increase in infection risk attributable to blood group is very small, paling in comparison to other risk factors.
Whatever Happened to Wastewater Monitoring?
In the US, wastewater monitoring for viruses like SARS-CoV-2 has great potential but is ineffective because it involves voluntary reporting by states. Most people in the US live in areas that don't monitor wastewater. Our northern neighbors in Canada, specifically Peel, Ontario, provide evidence that wastewater monitoring truly can be an early warning for increased infections. Investigators reported that wastewater levels predicted very reliably 1 day before the rise in infections and 4 days before a rise in hospitalizations during the omicron period of November 2021 to June 2022. At this point I'm not sure if the US has the resources to implement wastewater virus monitoring on a larger scale.
Better Evidence for MIS-C Treatment
The multi-system inflammatory syndrome in children is still difficult to diagnose precisely. Thankfully MIS-C seems less common in today's covid era with omicron dominance and high levels of antibody in the population. Now we have some better guidance for immunomodulatory therapy for MIS-C. This meta-analysis suggests that the combination of intravenous immunoglobulin plus glucocorticoid therapy improved cardiovascular dysfunction better than either agent alone. The study was very well done but had to rely heavily on nonrandomized cohort studies which introduces a great degree of bias in the results. We missed a chance by not conducting large RCTs of MIS-C treatment early in the pandemic.
Understanding Grendel
I needed to consult Wikipedia and other Cliff Notes-like versions of Beowulf to understand Gardner's book. As with everything I read, I think about what, if anything, might apply to me. With Grendel and Beowulf it was relatively easy. When faced with dramatically different perspectives, say for example pandemic deniers or anti-vaxxers (Grendel) versus traditional science and medicine (Beowulf), it's a good idea to try to see things from the opposing perspective. If one can do this without resorting to raised voices or worse, it's possible to have a meaningful dialog and even occasionally change minds, even my own! Next time you see me, look for Grendel perched on my shoulder. For those less prone to wild fantasies I recognize this is quite a stretch, but regular readers are accustomed to my tangents.
