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I finished a wonderful novel last week; among other things, it reminded me of the beauty, complexity, and destructive forces in nature, certainly applicable to infections, pathogens, and vectors of disease.

The past week saw more publications than I could cover in depth (or that readers could tolerate, probably), so I had to narrow things down even more than I usually do. If you're feeling particularly adventuresome, some of the topics I excluded pertain to a new phase I Chlamydia vaccine trial that could prove to be a breakthrough eventually, more advice on use of the new pentavalent meningococcal vaccine, an in vitro study suggesting nasal epithelial properties account for less severe covid disease in children, and a tularemia outbreak in Utah beavers. I also left out the growing Salmonella outbreak linked to organic basil, though I did alert one of my sons who often shops at a store featuring the tainted product. Here's what made the cut this week.

Respiratory Disease Transmission is Not Binary

Most things in biology and medicine aren't binary, even if we tend to reduce our thinking to that level to simplify things. For example, most lab tests aren't just positive or negative, even though they are reported that way. The cutoff between those two choices are made to maximize specificity and sensitivity of the tests, but they don't necessarily work for all circumstances.

The World Health Organization provided an important new proposal for changing our longstanding terminology for spread of respiratory infections as either droplet or aerosol (airborne). It's just not that simple, as SARS-CoV-2 painfully taught us. I found I couldn't improve on WHO's explanation of the complexity of pathogen transmission through the air, so here it is verbatim with some highlights in red that are mine:

The following descriptors and stages have been defined by this extensively discussed consultation
to characterize the transmission of pathogens through the air (under typical circumstances):

  • Individuals infected with a pathogen, during the infectious stage of the disease (the source), can generate particles containing the pathogen, along with water and respiratory secretions. Such particles are herein described as potentially ‘infectious particles’.
  • These potentially infectious particles are carried by expired airflow, exit the infectious person’s mouth/nose through breathing, talking, singing, spitting, coughing or sneezing and enter the surrounding air. From this point, these particles are known as ‘infectious respiratory particles’ or IRPs.
  • IRPs exist in a wide range of sizes (from sub-microns to millimetres in diameter). The emitted IRPs are exhaled as a puff cloud (travelling first independently from air currents and then dispersed and diluted further by background air movement in the room).
  • IRPs exist on a continuous spectrum of sizes, and no single cut off points should be applied to distinguish smaller from larger particles, this allows to move away from the dichotomy of previous terms known as ‘aerosols’ (generally smaller particles) and ‘droplets’ (generally larger particles).
  • Many environmental factors influence the way IRPs travel through air, such as ambient air temperature, velocity, humidity, sunlight (ultraviolet radiation), airflow distribution within a space, and many other factors, and whether they retain viability and infectivity upon reaching other individuals.

WHO still proposes a somewhat binary system of IRP spread, with "airborne transmission/inhalation" denoting pathogens which can spread at both short and longer distances, depending on various factors, versus "direct deposition," e.g. someone sneezes on you. It still may be confusing, but this is an important attempt to get past somewhat misleading advice such as a establishing a standard 6-foot distance between persons waiting in line.

Children and Adolescents Likely Still Benefit From Covid Vaccination

CDC has an update on covid vaccine effectiveness and durability, looking at the original monovalent vaccines over the time period from mid-December 2021 to late October 2023. Two doses of vaccine were 52% (95% CI 33%-66%) effective against hospitalization in the 5 - 18 year-old age group if vaccines were received no more than 4 months prior to hospitalization. From 4 to 12 months, protection against hospitalization waned significantly to 19% (95% CI 2%-32%). The report doesn't mention children less than 5 years of age, I suspect because vaccine authorization occurred later, numbers vaccinated are too small, and hospitalization was too uncommon to give reliable numbers.

Vaccine Adverse Events: New Numbers and a Terrific Interactive Web Site

The National Academies of Science, Engineering, and Medicine published new reports on adverse events from covid vaccines as well as an assessment of shoulder injuries from all vaccine administrations. The reports are excellent, but I fell in love with their web site. The NASEM group used levels of evidence to summarize current knowledge about various vaccine adverse events. The categories are evidence that a) establishes a causal relationship; b) favors acceptance of a causal relationship; c) inadequate to accept or reject a causal relationship; or d) favors rejection of a causal relationship. (Certainly this is far from a binary categorization!)

For covid vaccination they looked at six categories of adverse events: cardiac and vascular, female infertility, hearing conditions, immune-mediated events, neurologic events, and sudden deaths. The interactive web site allows you to pick and choose among various topics and subtopics and vaccines. Here's what the portion on myocarditis looks like:

Here's a look at acute biceps tendinopathy from vaccine administration in general:

You can also access the pdf version of the report (note it is a pre-publication proof, could contain some typos) to look at the summary and/or more details.

A Significant Change for Syphilis Screening From ACOG

I'm thrilled to see new recommendations for syphilis screening of pregnant people from the American College of Obstetricians and Gynecologists. I feel like my practice is a congenital syphilis quagmire right now. This updated recommendation gets away from the risk-based approach for screening which has always been a bit vague and clearly less useful with the resurgence of syphilis in the US. Now, every pregnant person should have syphilis testing 3 times: at the first prenatal visit, during the third trimester, and at birth. Previously a pregnant person with good prenatal care could escape with being screened only once early in pregnancy, a practice that would miss recent infection or infection acquired later in pregnancy. They also remind us that 40% of congenital syphilis occurs in infants whose mothers did not receive prenatal care; syphilis screening should be considered for pregnant people at every interaction with the healthcare system, such as emergency or urgent care visits.

Fake News From USDA?

Because of the avian flu concerns in the US, I've been trying for the first time to use alerts from the US Department of Agriculture on the status of avian influenza in wildlife and domesticated animals, including the recent importance of dairy animals. So far the alerts aren't telling me much, just clogging my in box with unhelpful information. So, I was a bit dismayed to see a recent NY Times article criticizing USDA transparency. Unfortunately the article requires a subscription, but it mentions an "obscure" USDA update (that I didn't receive) mentioning influenza A H5N1 further spreading among dairy cow herds and from there to poultry. More distressing to me is a claim in the Times article stating that asymptomatic infections have been discovered in a herd, but not yet reported by USDA; this is important since screening advice for dairy farmers currently is focused on symptoms in the cattle, with no screening of healthy-appearing cows. Perhaps USDA hasn't reported this asymptomatic infection possibility because it hasn't been verified, but one hopes they will be more transparent (and provide better updates) than they have so far. CDC learned a lot about public communication and transparency during the covid pandemic that should inform communications from USDA and other government agencies that we depend on.

Measles

Only 4 new cases reported in the last week, hoping we stay in this lull for a good while.

Elm Beetle Romance

That novel I finished recently was Daniel Mason's North Woods; it's had mixed reviews but I thoroughly enjoyed it. The author happens to be a psychiatrist, and this recent offering from him is an entertaining look at the happenings in a house in rural Massachusetts over several centuries. I had a great chuckle from a brief description of Dutch elm disease complete with a steamy sex scene involving elm bark beetles. Maybe I need to get out more.

Even though Maryland wasn't in the full eclipse path, I miraculously located my eclipse glasses and enjoyed Monday's event. It easily overshadowed last week's relatively quiet collection of infections.

Newer Covid Publications

CDC gave us more reassurance that cardiac events associated with covid vaccination are mild. For the period June 2021 - December 2022, investigators looked at Oregon death certificate data in adolescents and young adults (16 - 30 year-olds). They found 40 deaths, 3 of which occurred < 100 days following receipt of covid vaccine, a time period when vaccine-associated myocarditis/pericarditis occurs. Of those 3, 2 individuals had underlying disease (one had mitral stenosis associated with chronic respiratory failure, the other congestive heart failure due to hypertension, with comorbidities of morbid obesity, type 2 diabetes, and obstructive sleep apnea). The other person died of "undetermined natural cause" 45 days after vaccination; toxicology results showed aripiprazole, ritalinic acid, and trazodone, presumably medications the individual was receiving but apparently not definitively explaining a cause for death. To most scientists this is further good news, but I'm sure anti-vaxxers will somehow spin this as a negative. Below is the big picture:

German investigators reported success of a program using pooled SARS-CoV-2 PCR testing to allow children to remain in day care versus quarantining after covid exposure, which they termed a "test-to-stay" approach.

The investigators estimated that. over a 30-week period, they avoided between 7 and 20 days of quarantine per eligible child. The study was performed from March 2021 to April 2022, at a different state of immunity and variants than we are experiencing today but still helpful to strategize when we hit the next big outbreak.

More on Bird Flu/HPAI

Highly pathogenic avian influenza news has calmed down a bit, but the viruses are still out there. We are up to 21 dairy herds with outbreaks according to USDA:

As of April 10, CDC reports widespread detections in wild birds with sporadic outbreaks in poultry flocks, sporadic infections in mammals, and still just the 2 human infections.

Measles

Not as many new cases now, with Illinois and Florida retaining the dubious distinction as leading all states this year. The national total stands at 121.

CDC reported that most US measles outbreaks from 1/1/20 through 3/28/24 were triggered by unvaccinated US residents returning from foreign travel. This is a good reminder for frontline clinicians to advise people planning foreign travel this summer to ensure their families have not only up-to-date immunizations but also early measles immunization for infants and toddlers who otherwise have not received 2 doses of MMR.

I also happened upon a link for assessing measles outbreak risk in US communities. I resisted the temptation to copy the entire page here, please check out the link. Here's a few highlights:

So, about 29% of US communities are at risk for small or medium outbreaks, with 1% at risk for a large outbreak. Even within communities with the same vaccination coverage, outbreak risk can vary if they have pockets of unvaccinated people.

And a look at outbreak modeling risks for measles outbreaks after one measles case is introduced in a school, according to vaccine coverage rates. (Note these numbers apply for situations where no post-exposure preventive measures are instituted. Risks go down if established interventions are applied.)

Here's the latest (2022-23) geographic measles vaccine coverage data.

Fingers crossed for measles to continue to slow down, though I'm predicting another blip around travel season.

See you next week!

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.

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.

Those words written by a famous children's author in 1988 remain relevant today; details to follow after a few mentions of other pediatric infectious disease news from the past week.

Covid Serology Update

The Infectious Disease Society of American updated their guidelines for use of covid serology testing. It is the 4th update since the pandemic began, but there isn't much new here. Currently over 95% of the US population has evidence of immunity either from natural infection, vaccination, or both. Serologic testing of individuals mostly is discouraged because it won't provide any useful clinical information to manage an individual's situation. About the only use might be to check immunity in immunocompromised individuals to help decide if immunotherapy could be warranted for prophylaxis or for treatment of active infection.

Covid in Young Infants

Early in the pandemic, most very young infants diagnosed with SARS-CoV-2 infection were hospitalized. This was due to a combination of the usual practice for febrile infants less than 1 month of age as well as the uncertainty of infection outcomes in this age group. I recall from my clinical experiences that it appeared that most young infants actually did well, though there were exceptions. Finally we have a study that gives us some more detailed data about young infants early in the pandemic. It is a secondary analysis of a prospective global study that recruited children presenting to pediatric emergency departments with illness and tested for covid. The study design allows for much more detail (and presumably more validity) than the other designs such as review of administrative data. The study (actually 2 studies combined) enrolled between March 2020 and February 2022. They ended up with 432 children testing positive for covid to compare with 616 testing negative. Clinical outcomes were generally more severe in the SARS-CoV-2-negative infants:

So, at least early in the pandemic, young infants with SARS-CoV-2 infection fared pretty well.

A Colorful Variant Update

Nothing new about this, but I admit to a strange attraction to colorful covid variant charts. I thought it was interesting to look back to see how the JN.1 variant progressed in the US.

The JN.1 shade of purple has been called "indigo purple" (hex #660999).

Varicella Misdiagnosis

A new CDC report suggests clinicians aren't too skilled in diagnosing varicella infections, perhaps because it is now much less common due to effective vaccination. The Minnesota Department of Health looked at suspected varicella cases from 2016 to 2023, a time when they implemented a new system for processing PCR testing of lesions. Of 208 suspected varicella cases, only 45% had positive tests; in vaccinated patients, the number dropped to 22%. They attributed this to unreliability of clinical diagnosis of varicella, especially in vaccinated patients, but I suspect other factors (improper specimen collection technique, testing unlikely varicella patients "just to be sure") may be contributory as well. Anecdotally I've certainly noticed how difficult the diagnosis varicella-zoster virus infection can be for younger clinicians who don't have the experience of seeing multiple cases in the pre-vaccine era.

Speaking of Misdiagnosis ...

I'm in my broken record mode again here. In case you've been hibernating or torporing, we're in the midst of a global measles surge. I read with alarm of a measles vaccine shortage in Canada. There are no signs of a similar shortage in the US; you can always check on US vaccine shortages at this CDC site. With spring break upon us now, and summer travels coming up, all of us need to brush up on measles diagnosis. Thankfully we have a lot of help.

Last Sunday, the CDC issued a Health Alert Network post with a number of useful links. The American Academy of Pediatrics provides a one-pager with great advice as well as a 5-minute video. Another source I've found very useful for years is from a now out-of-print textbook, Krugman's Infectious Diseases of Children. When I discovered libraries no longer carried it, I tracked down a used copy of the 10th edition (1998) released by a university library and have made continued good use of their black and white diagrams. Here's the clinical progression of illness, the key highlight here is the prodrome of a few days before the rash appears. This is very helpful in suspecting a measles diagnosis because the prolonged prodrome is very unusual in pediatric infectious exanthems.

Also useful is the development and distribution of the rash:

I failed to find a current global measles map so return to the CDC website to at least give a current view of US measles cases. For this calendar year we are now up to 64 cases spread over 17 jurisdictions.

Many clinicians may not remember that, though the first measles vaccine was approved for use in the US in 1961, it wasn't until 30 years later that a second dose was recommended. That was spurred by cases in the late 1980s appearing in vaccinated school children, the first major sign that a single dose wasn't sufficient to prevent outbreaks. That second dose was first recommended for 11-12 year olds by the AAP, subsequently dropped to the 4-6 year age group in 1997 to come into agreement with the CDC. Importantly, the interval between the 2 doses can be as short as 28 days for MMR and 90 days for MMRV vaccines, and early vaccination down to 6 months of age is indicated in special circumstances, such as for children who will be traveling internationally. Frontline pediatric providers need to be proactive in alerting parents planning international travel to ensure that their children ages 6 months and older are protected. Scroll down to the Special Situations section on the CDC immunization schedule notes.

Roald Dahl

I learned just recently that this famed children's book author lost a daughter to measles in 1962. He wrote 25 years later, "Olivia, my eldest daughter, caught measles when she was seven years old. As the illness took its usual course I can remember reading to her often in bed and not feeling particularly alarmed about it. Then one morning, when she was well on the road to recovery, I was sitting on her bed showing her how to fashion little animals out of coloured pipe-cleaners, and when it came to her turn to make one herself, I noticed that her fingers and her mind were not working together and she couldn’t do anything. 'Are you feeling all right?' I asked her. 'I feel all sleepy,' she said. In an hour, she was unconscious. In twelve hours she was dead.”

She had developed measles encephalitis. He wrote this in the late 1980s to encourage parents in the United Kingdom to accept a new MMR vaccine for their children (monovalent measles vaccine had been introduced in 1968 in the UK). He also wrote, “In my opinion parents who now refuse to have their children immunised are putting the lives of those children at risk. In America, where measles immunisation is compulsory, measles, like smallpox, has been virtually wiped out. Here in Britain, because so many parents refuse, either out of obstinacy or ignorance or fear, to allow their children to be immunised, we still have a hundred thousand cases of measles every year.”

Much has been written about Dahl's dark side (e.g. "an equal-opportunity bigot"), but I give him credit for trying to help children and their parents avoid the misfortune he and his family experienced.