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Published on 2 Comments on Bug Art

I hope everyone had a wonderful Thanksgiving holiday, I know I did. With 4 physicians and 2 other medical professionals at the the table this year, our family went through the usual dressing/stuffing discussions with risk of undercooking the stuffing resulting in higher salmonellosis risk. We remain asymptomatic.

Recently I watched a 3-part PBS series about the artist Frido Kahlo. It also featured her sometimes-husband, Diego Rivera, prominently; he was a better known artist than Kahlo for much of the 20th century. Little did I know, until a hot-off-the-presses review article, that he had a bit of microbiologic art featured in some of his works.

First, let's look at what's been going on, besides Thanksgiving, this past week.

Strep Throat Should Be Simple

Every now and then I go on a rant about strep throat. Of course sore throat is very common, and it sounds like a simple problem, but in fact it is one of the most poorly understood maladies I deal with. The combination of a common clinical problem with a pathophysiologic basis full of lacunae has resulted in generally poor management, most conspicuously in antibiotic overuse. The biggest problem is trying to determine someone who tests positive for GAS is just a streptococcal carrier who really has viral pharyngitis from someone with true streptococcal pharyngitis who would benefit from antibiotic treatment. With rare exceptions, identifying a streptococcal carrier is of no clinical utility and only serves to increase unnecessary antibiotic use. We badly need better diagnostic tools (both clinical and laboratory) as well as a better understanding of drivers of serious sequelae such as invasive disease and post-streptococcal arthritis, rheumatic fever, and glomerulonephritis.

Now we have a very intriguing study of essentially healthy children presenting with sore throat and then followed as a prospective cohort for 2 years, looking specifically at antigen testing, throat culture, streptococcal antibody levels, and outcomes. It was mainly designed to provide a framework with which to test upcoming vaccines for group A streptococcus - if you don't have accurate inclusion criteria and outcomes, it's pretty tough to measure vaccine effectiveness. I want to also mention here that of the 8 authors, only 1 was an actual clinician; the rest were all employees of a pharmaceutical company that develops vaccines. Normally that degree of for-profit pharma involvement in a trial would raise concern for implicitly biased interpretations of the results, but in this case we don't have a vaccine product involved in the study so perhaps less for me to fret about.

Children could be enrolled if they were from 3 to 12 years of age and did not have circumstances that could alter conclusions, including no documented group A streptococcal infections in the 6 months preceding study entry. Here's the protocol at study entry at the time of presentation with sore throat (RADT denotes a rapid antigen test for GAS):

Study subjects then had healthy visits at 3-month intervals for the remainder of the 2 years, as long as it was at least 6 weeks following sick visits. At the healthy visits they had throat culture for GAS, but not RADT, obtained. Serology for the sick visits included blood for antistreptolysin O, anti-DNase B, and antistreptococcal C5a peptidase antibodies. If GAS pharyngitis was diagnosed at sick visit 1, the children were treated as per standard by their clinician.

Definitions are important here. A GAS carrier was defined as a positive healthy visit GAS culture plus a positive RADT or culture at sick visit 1 that remained positive at sick visit 2 which occurred 7-10 days after completion of antibiotic therapy for the sore throat event. The researchers evaluated several definitions for GAS pharyngitis which I copy here:

I provide a lot of background for the study methods because they seem very well considered to me, plus I think it is helpful for clinicians to consider all of these possible case definitions when evaluating children with pharyngitis.

Now for the results. First, streptococcal antibody measurement is mostly useless to distinguish true infection from carrier state. That could have been predicted from multiple prior studies but is particularly important in monitoring antibody response in vaccine trials.

Don't look to this study to change your clinical practice if you already follow guidelines for management of GAS pharyngitis. What it does show is how difficult it will be to design trials for future GAS vaccine effectiveness. In the 1960s, a GAS vaccine likely caused an increase of acute rheumatic fever-like illness in vaccine recipients, and GAS vaccine development has been appropriately cautious since that time. GAS vaccine safety issues have been reviewed recently.

Also be aware that I had a few questions about the study that weren't addressed in the publication or the accompanying online supplemental information. I've emailed the first author, the one clinician in the study, and if I hear back I'll provide updates.

It's Beginning to Look a Lot Like ...

.... winter respiratory virus season. RSV, influenza (sorry, at the time I'm writing this we have no new FLUVIEW updates since the week ending November 11), and to a lesser extent wastewater covid all are on the upswing,

It doesn't qualify as a tripledemic yet, but stay tuned.

The Verdict on Last Season's Flu Vaccine

The 2022-23 influenza season was a bad one for pediatric hospitalizations, but we now have some final data on how well the influenza vaccine prevented such episodes.

The vaccine effectiveness is pretty good, in line with other seasons for the most part. The low vaccination rates are another key takeaway; I wish this would improve, but I'm not optimistic given the current upswing in vaccine hesitancy.

Holiday Season Puzzler

Here's a glimpse of Figure 2 from the Rivera review article. As you emerge from what I hope was a wonderful Thanksgiving holiday, see if you can identify the types of organisms that are depicted.

Published on Leave a comment on Lots of Thanks This Year

I didn't have any trouble thinking of things to be thankful for this Thanksgiving-time. That might seem odd given the horrific events on the world stage now, and I don't mean to minimize that, but gratitude can coexist with dismay.

First, let's get caught up on this week's ID happenings.

Disappointing Measles News

Measles is probably the most easily transmissible human infection known; a high level (probably 95%) of population immunity is needed to prevent outbreaks. Not surprisingly, a breakdown in immunization rates during the COVID-19 pandemic likely is to blame for increases in measles cases worldwide, as reported last week by the CDC. Concomitant with a decrease in measles-containing vaccine coverage from 86 to 81%, measles cases increased 18% (7.8 million to 9.2 million) worldwide from 2021 to 2022; deaths increased from 96,000 to 136,200. Still, and here's the thankful part, vaccination likely prevented 57 million measles deaths from 2000 to 2022. Here's hoping we can get our global immunization campaigns back on track.

2024 CDC Recommended Immunization Schedules Are Available

Even earlier than advertised, CDC has posted the 2024 immunization schedules. Primary care providers should study these closely due to some complex changes, particularly for pneumococcal and meningococcal vaccines. The AAP has posted a summary of key changes (click on the PDF link). As an aside, I'm a bit irked by what CDC and others call "shared clinical decision-making." Here's CDC's tool for SCDM for meningococcal group B vaccine:

I'm not a primary care provider, but I don't see a lot of help for busy frontline practitioners here. What we really need are more details about choices parents and patients need to consider. Specifically, what are the risks of not getting the vaccine versus those being vaccinated? As stated in the table, meningococcal B infections are relatively rare in the US, so vaccination isn't going to prevent much disease or mortality even with a highly fatal infection. The risks are different depending on individual circumstances. Are frontline providers supposed to have these numbers at their fingertips? Maybe the CDC or AAP will provide them. (Or, if not, maybe I will!)

MIS-C Cardiac Follow-Up

Multisystem inflammatory syndrome in children (MIS-C) following covid infection is very uncommon currently, but we shouldn't forget about monitoring children as they recover from MIS-C. A group at Children's Hospital of Los Angeles reported that even children who did not have clinical cardiac involvement during their acute illness still had some evidence of cardiac injury at the 6-month followup period. Most of the report deals with laboratory, imaging, and other testing, but of the 69 patients evaluated at 8 weeks 15 had clinical symptoms such as chest pain, palpitations, exertional dyspnea, or fatigue. The rate of clinical symptoms was actually lower in the group with no initial myocardial injury, although the difference was not statistically significant. The bottom line: make sure all MIS-C patients have good cardiology followup.

Variations in Influenza Antiviral Use

A group from Vanderbilt reported wide variation in prescribing practice for influenza antivirals during the period 2010-2019 (so, not affected by the pandemic). It is an administrative database study, a study design type that has inherent inaccuracies due to how administrative data is collected. In general, however, a wide variation in practice is an indication that something isn't right. Guideline-concordant compliance was low, for example <40% in children less than 2 years of age, a high risk group. I would have liked to have seen how flu vaccine status affected antiviral use since vaccination greatly lowers risk for severe adverse outcomes, but apparently the database did not contain that information. This is another opportunity for shared clinical decision making with parents; what are the specific rates for infection, hospitalization, etc versus medication side effects (primarily vomiting with oseltamivir) for an individual child, based on their risk factors? That's what a frontline health provider needs when discussing whether to treat a child for influenza.

The "New Normal"

I mention this catchphrase only to bury it. Not only does it seem nonsensical to me, it also is beyond retirement age. Some might wish to apply this catchphrase to the upcoming winter season. I'm strangely thankful/hopeful for this because it now appears we may get to see what a typical respiratory virus season looks like in the post-pandemic era. We haven't seen any weird covid upticks early on, and RSV looks more typical so far without the very severe season we saw last year. Flu may be starting to increase, similar to pre-pandemic seasons. Of course, all of the respiratory virus seasons vary somewhat from year to year. Will covid settle into just another winter respiratory virus?

FLUVIEW is back in business, and the map is heating up especially in the South.

Remember that this is a map of "influenza-like illness" so can capture other respiratory viruses. However, covid wastewater tracking hasn't had much of an uptick.

RSV-NET continues to show increase primarily in younger children, not matching last year's peak but possibly similar to prepandemic waves.

Happy Thanksgiving

I was looking around for something uplifting and fun to mention and happened on "Thanksgiving" by Edgar Albert Guest. Here's an excerpt:

"Greetings fly fast as we crowd through the door

And under the old roof we gather once more

Just as we did when the youngsters were small;

Mother’s a little bit grayer, that’s all.

Father’s a little bit older, but still

Ready to romp an’ to laugh with a will.

Here we are back at the table again

Tellin’ our stories as women an’ men."

I had never read anything by Guest, but I was sold on him when I read his Wikipedia page. Anyone who merits mention by Edith Bunker from "All in the Family," Lemony Snicket, Mad Magazine, and Benny Hill is my kind of guy. Furthermore, Dorothy Parker of Algonquin Round Table fame had the best line: "I'd rather flunk my Wassermann test than read a poem by Edgar Guest." I think maybe she wasn't a fan, but at least she knows her 1950s syphilis testing.

Wishing everyone a Safe and Happy Thanksgiving.

Published on Leave a comment on I Should Have Listened to Myself

Last week I was a bit obsessed with all the leaves around my house, both on the ground and still in the trees. With a neighborhood leaf collection looming and many leaves still to fall, I decided not to rake that day. The next day I reversed my stance, which was a bad idea.

On the COVID Front

Although we aren't seeing much of a surge so far (see Tripledemic below), I did come across a few items to mention.

First, FDA issued an alert about potential dosage errors with the Moderna vaccine for children 6 months through 11 years of age. The standard dosage is 0.25 ml, but apparently the single dose vials contain "notably more" than this amount. So, if one draws up the entire contents of the single dose vial and administers it, the dose will be too high. Try as I might, I was unable to determine how much above 0.25 ml "notably more" is. So far the overdosage hasn't been shown to cause any harm. Please alert your staff to this.

On the topic of Multisystem Inflammatory Syndrome in Children, a prospective cohort study in the Netherlands suggests that MIS-C is lessening recently, possibly related to prior immunity. This fits with other reports, mostly anecdotal.

Finally, and consider this a very preliminary observation, researchers in China have noted an apparent increase in situs inversus diagnosed with prenatal ultrasound following lifting of covid restrictions in that country.

I'm advising caution in interpreting this study because 1) it is a short letter to the editor so methodologic details are a little sparse (supplementary online appendix helps); 2) funny things can happen when an epidemiologic blip is noticed that then triggers a look back - although the authors claim their protocols for performing sonography didn't change, all sorts of bias can affect the data in this setting; and 3) no one else has reported this association previously. I'm sure we'll see further refinement on this topic from these and other investigators in the coming months.

Some readers may have noticed I haven't mentioned anything about SARS-CoV2 variants for a while. They are still out there, changing rapidly as usual, but I won't comment much until/unless we see emergence of a variant dramatically different in its ability to alter epidemiology of disease, either by evasion of prior vaccine and infection immunity or with increased virulence.

New Infant Hepatitis C Screening Recommendations

CDC has issued new screening guidelines for infants born to mothers with hepatitis C, which should help identify infants at risk earlier. The entire document is very well written and informative. Expect updates to appear in the Red Book and from other organizations. Here is the bottom line for primary care providers, including a definition of perinatal exposure.

For a child not screened in early childhood:

Hepatitis C testing is a bit confusing to many providers; don't hesitate to seek assistance from your friendly neighborhood pediatric ID or GI provider!

Tripledemic Update

RSV continues, but we have yet to see any notable increases in flu or covid.

RSV-NET still shows an increase in hospitalizations nationally, ages 0-4 years shown in purple.

The FLUVIEW map is similar, though note this is tracking "influenza-like illness" which will be contaminated with other respiratory viral infections.

Biobot wastewater monitoring is at about the same level, still far below the January 2022 surge.

I continue to focus on wastewater data for SARS-CoV-2 due to the decrease and vast variability in tracking infections, hospitalizations, and deaths now compared to during the pandemic.

Autumn Thought

As I was finishing sweeping and raking leaves and carting them to the curb for pickup, a big wind came up. Within about 10 minutes, the areas I had just cleared looked exactly the same as before I started. The only change was that big maple tree outside my window now had significantly fewer leaves clinging to branches. At least I got a little exercise.

Langston Hughes, one of my 2 favorite American poets (Wallace Stevens being the other), wrote a short poem in 1921 entitled Autumn Thought:

Flowers are happy in summer.

In autumn they die and are blown away.

            Dry and withered,

Their petals dance on the wind

Like little brown butterflies.

And... Happy End of Daylight Savings Time!

Published on Leave a comment on To Rake or Not To Rake

A lot going on in the world of infectious diseases this past week, enough to challenge my ability to sort out and explain the key points. That's probably why my mind, and eyes, keep drifting to the window next to my desk. The neighborhood leaf pickup is coming any day now, and many leaves cover the ground. The number of fallen leaves is still far less than remain on the old maple tree just outside the window. Yes, it's too early to rake, I would just need to do it again in another week.

Here's my stab at summarizing recent ID events.

RSV and Nirsevimab Shortage

CDC issued a HAN (Health Alert Network) advisory statement on October 23 with a plan for prioritization of nirsevimab use in the face of limited supply.

I won't attempt to summarize everything here because the recommendations are detailed and depend highly on individual circumstances impacting nirsevimab access; please read the advisory. The 100 mg dose is the most severely restricted, and practitioners should not combine 2 50 mg doses to make up the difference because you are essentially depriving 2 younger/smaller children from access in order to treat 1 other child. Note that palivizumab (Synagis) is still available and is the go-to product for infants 8 - 19 months of age, the same as in previous RSV seasons.

At last week's Advisory Council on Immunization Practices (ACIP) meeting (see more below), the nirsevimab company representative completely avoided answering a request to provide details for the cause of the shortage, other than to invoke a supply versus demand problem. I'm hoping those details appear down the road so mistakes like this can be prevented in the future.

Remember COVID-19?

I hope nobody has forgotten, but never underestimate our short attention spans. Thankfully things are relatively calm compared to pandemic times.

I felt the lay press got things a bit wrong when reporting findings of a study by FDA and others regarding safety of monovalent covid vaccines given to children before early 2023 (i.e. NOT the current vaccines). Unfortunately the report has not been peer-reviewed, but it appears pretty sound from my brief reading. The risk of myocarditis/pericarditis in adolescent boys was pretty much the same as we've heard about all along. Also mentioned was seizure risk in younger children, and this part was over-hyped by some news agencies. The association merits further study, but currently is very uncertain: "...seizures/convulsions signals were detected following vaccination with BNT162b2 and mRNA-1273 in children aged 2-4/5 years. However, in a post-hoc sensitivity analysis, the seizures/convulsions signal was sensitive to background rates selection and was not observed when 2022 background rates were selected instead of 2020 rates." The exact numbers were 72 children with seizures, most fulfilling the case definition of febrile seizures, out of 429,119 doses administered to that age group. Thus, it is very close to the background rate of febrile seizures, without vaccination, in that population.

Tripledemic Status

Well, more like a weak monodemic now, with RSV still the only one of our RSV/Influenza/Covid triumvirate to appear in appreciable numbers in most places. RSV-NET shows some hospitalizations in young infants below, but note that hospitalizations are only the tip of the iceberg for infections.

FluView activity is similarly low in most locales.

Biobot wastewater tracking for covid remains low.

New Immunization Schedules for 2024

As mentioned above, the ACIP met October 25 and 26 to cover a variety of subjects and reveal proposed immunization schedules for 2024 which were approved. This approval is awaiting some tweaking and then final signoff by the CDC director. The new schedules will have many new options, which is both good and bad. It's always nice to have more choices, but at the same time those choices create new complexities that aren't easy to explain; CDC doesn't have a great track record for making recommendations understandable. Potential changes include vaccines for COVID-19, influenza, meningococcus, mpox, pneumococcus, polio, and RSV (monoclonal antibody and vaccine). Release is planned for January 2024, earlier than usual.

Pediatric healthcare providers should take note of proposed new mpox vaccine recommendations, now just applying to age 18 and older but likely to eventually include ages as young as 12 years once NIH trials are completed, perhaps as early as next year. Like most outbreaks/epidemics/pandemics, mpox has evolved from the 2022 epidemic into a 2023 endemic problem now at about 1-4 cases per week on average.

Because of this, and the fact that a highly effective and safe vaccine is available, the new guidelines likely will recommend immunization for those at high risk:

Gay, bisexual, and other men who have sex with men, transgender or nonbinary people who
in the past 6 months have had one of the following:

  • A new diagnosis of ≥ 1 sexually transmitted disease
  • More than one sex partner
  • Sex at a commercial sex venue
  • Sex in association with a large public event in a geographic area where mpox
    transmission is occurring
  • Sexual partners of persons with the risks described in above
  • Persons who anticipate experiencing any of the above

We will also see new recommendations for pneumococcal vaccine now that a 20-valent pneumococcal conjugate vaccine is approved. PCV13 will phase out and infant immunization will include just PCV15 or PCV20. The 23-valent pneumococcal vaccine also will phase out, except perhaps for a stockpile kept for use in immunologic diagnostic testing.

Covid vaccination will be a little easier for young children, with clarifications for which vaccines to use for children undergoing age transitions in the midst of vaccine cycle as well as greater allowance for interchangeability of vaccines (e.g. administering Pfizer vaccine when previous vaccine was Moderna) for children 6 months through 4 years of age:

COVID-19 vaccine doses from the same manufacturer should be administered whenever recommended. In the following circumstances, an age-appropriate COVID-19 vaccine from a different manufacturer may be administered:

  • Same vaccine not available at the vaccination site at the time of the clinic visit
  • Previous dose unknown
  • Person would otherwise not receive a recommended vaccine dose
  • Person starts but unable to complete a vaccination series with the same COVID-19 vaccine due to a contraindication

The changes for meningococcal vaccination are the most confusing. A pentavalent vaccine was approved recently by FDA for use as a 2-dose regimen for ages 10 through 25 years. The confounding factor for meningococcal vaccination is that the disease is relatively uncommon, particularly for serogroup B where we see only a handful of cases annually. Furthermore, vaccine immunity wanes fairly quickly following group B vaccination, and we are potentially faced with healthcare offices needing to stock 3 different meningococcal vaccines to cover all circumstances. Here are the current recommendations for meningococcal vaccination:

Here's a look at the serogroup distribution by age (June 2023 ACIP meeting, presentation 3 slide 9 for meningococcus):

How best to add in the pentavalent vaccine? Just using that vaccine alone isn't a good idea. Trying to incorporate immunization against group B into the current schedule that starts at age 11 is likely too early to be effective. ACIP has been struggling for several months to come up with a plan for meningococcal vaccination that takes into account the relative rarity of the disease as well as the need to provide a pragmatic plan that can be implemented in diverse healthcare settings. They focused on 3 policy questions that were debated by working groups over the past several months:

PICO 2 was deemed unfavorable for a variety of reasons. We are left with deciding how best to use the pentavalent vaccine for situations 1 and 3, knowing that stocking 3 different meningococcal vaccine products may not be feasible for many practice settings. I expect continued tweaking of the options before we see the final guidelines in January, but it appears that routine immunization will still be recommended at age 11-12 years with second dose at 16 years. Group B vaccination options will variously allow use of the monovalent or pentavalent products, but it may be that the pentavalent product will be recommended for a slightly different age range (16 - 23 years) than what was approved by FDA (10 - 25 years). Regardless, the Menactra vaccine (covering groups A, C, W, Y) will be withdrawn so at least some simplification there.

A concluding disclaimer to this section: all we have now from ACIP are proposed changes. They are not approved and very likely will undergo some changes before we see them in print. Please don't act on the above until we have the updated guidelines from CDC.

Staring Out the Window Again

You can perhaps understand my tendency to wander after reading the section above. The meningococcal vaccination options are almost endless, and I didn't necessarily agree with the way the discussions were going at the ACIP meeting.

The title of this posting is a lame riff on Shakespeare, and his Sonnet 73 mentions leaves prominently. However, it is primarily a poem about aging and I didn't necessarily want to be reminded of that! I found a more playful ode to autumn in a poem by James Whitcomb Riley; he has a children's hospital named after him although he was a very complex individual who suffered from alcoholism and wasn't exactly a model citizen. His poems often are written with a child-like voice and lend themselves well to reading aloud.

"But the air’s so appetizin’; and the landscape through the haze

Of a crisp and sunny morning of the airly autumn days

Is a pictur’ that no painter has the colorin’ to mock—

When the frost is on the punkin and the fodder’s in the shock."

Published on Leave a comment on Yellow Jack in the US? Are You Kidding Me?

It's nice to be back after my brief website repair hiatus. Please let me know if you have any problems or have any suggestions for the website. I'll continue to work on design issues.

I won't attempt to cover all the issues in pediatric infectious diseases appearing during the hiatus. Needless to say, at lot happened, mostly old news by now. Some newer things I won't mention because they appear only in abstract form at national meetings, such as this month's ID Week (Infectious Diseases Society of America and other ID groups) and the American Society for Tropical Medicine and Hygiene. I have seen dramatic changes from the time data are presented at a meeting, which can be preliminary and incomplete, to the final publication or lack thereof. I've become averse to propagating that type of information source.

Yellow jack is another name for yellow fever; it takes its name from the yellow nautical flag that alerted others that yellow fever was on board. A variation of this flag is still used today to alert other ships about health issues on board. You might want to brush up on your yellow fever knowledge now, keep reading if you're intrigued.

Nirsevimab Supply Chain Flop

This isn't news to any practicing primary pediatric healthcare provider. The supply of the newly-approved long-acting monoclonal antibody preparation to prevent RSV infection for all infants has hit a major snag: demand has far outstripped supply. Maybe we will eventually hear the true story of what happened, but basically we are dealing with a single manufacturer who couldn't produce enough product. Even some hospitals aren't able to get a supply to administer to newborns at the time of discharge.

The AAP has a nice RSV page that healthcare providers may find useful, as well as an October 17 webinar with practical strategies. Remember that maternal RSV vaccination at 32-36 weeks gestation is another option to encourage; talk to preganant people visiting your practices. Palivizumab (Synagis) is still available for high risk infants.

Tripledemic Update

We're certainly not anywhere close to a tripledemic at present. Only RSV seems to be on a significant upswing:

Flu season hasn't yet started for most of the country. COVID-19 disease is much more difficult to track now that our tracking methods have changed so dramatically from the pandemic area. I look to wastewater reports as the most consistent indicator over time, and they suggest that we did not have a big spike this fall.

Future Pandemic Preparedness

The Journal of Infectious Diseases finally got around to publishing a supplement on vaccine and monoclonal antibody development for potential future viral pandemic pathogens. It was put together from presentations at a meeting in 2021. Here's a quick overview of the types of pathogens considered:

Comparison of pandemic potential and countermeasures for viral families known to infect humans. Viral families were categorized as having either low/moderate or high pandemic potential and low/moderate or high levels of existing resources and countermeasures. Cross-comparison revealed 10 viral families with high pandemic potential and low/moderate existing resources or countermeasures upon which the National Institute of Allergy and Infectious Diseases will focus its pandemic preparedness activities. Asterisks denote existing vaccine solutions for some viruses in that family; boldface type, potential vaccine solutions for the entire virus family; shaded box, viral families chosen for prototype pathogen selection.

I'm sure many of these names except for Coronaviridae are unrecognizable to most physicians, and several at best are vague even for infectious diseases specialists. Orthomyxoviridae include influenza viruses. Let's hope research funding comes through for the entities in that lower right box.

Yellow Fever

You probably haven't thought much about yellow fever unless you've considered travel to an endemic area, either for yourself or for patients in your practice. We have an effective vaccine available, but it is a live virus vaccine. Risks for vaccine side effects increase with age greater than 60; I actually received yellow fever vaccine for travel when I was in this high risk group; more on that later.

A recent Perspective essay in this week's New England Journal of Medicine raised the possibility of yellow fever reappearing in the US, particularly in the southeastern United States. This is already a problem with other mosquito-borne infections like dengue, chikungunya, and Zika viruses. (Note these are in the family Flaviviridae, also included in the gray box above.) The vectors for yellow fever, Aedes aegypti and A. albopictus, are well represented in the US, and their range is increasing as our climate warms.

Yellow fever is endemic in some parts of South America and Africa, and its range appears to be spreading in recent years. (The maps below are a few years old, updated WHO country recommendations usually are published in November.)

Diagnosing yellow fever without a travel history will be very difficult in most instances. In about 85% of those infected, the clinical presentation is a self-limited, nonspecific febrile illness with chills, myalgia, headache, and some GI symptoms lasting about 3 days. An unlucky 15% have a more biphasic presentation with the second stage appearing after around 48 hours of improvement and characterized by more severe symptoms including jaundice, renal failure, coagulopathy, and other life-threatening problems. At that stage the diagnosis might occur to an astute provider and diagnostic testing can be obtained. No specific antiviral therapy is available.

Yellow fever vaccine is highly effective, and a single dose confers life-long immunity. It is relatively safe, but there are rare severe side effects. These severe reactions are 3- to 4-fold higher in vaccine recipients over 60 years of age:

Yellow fever vaccine associated neurologic disease (YEL-AND; mostly encephalitis, Guillain-Barre syndrome):

  • over 60 years of age = 2.2 cases per 100,000 doses of vaccine administered
  • less than 60 years of age = 0.8 cases per 100,000 doses of vaccine administered

Yellow fever vaccine associated viscerotropic disease (YEL-AVD; similar to severe infection itself with approximately 50% mortality):

  • over 60 years of age = 1.2 cases per 100,000 doses of vaccine administered
  • less than 60 years of age = 0.3 cases per 100,000 doses of vaccine administered

I was over 60 years of age when my travel to Ethiopia caused me to consider yellow fever vaccine. My reasoning wasn't based on the 3- to 4- fold increase in risk, which is a relative risk increase, but rather focused on the absolute risk. This is a topic I've revisited many times in this blog; it has immediately applicability to vaccination of any type but especially for COVID-19 and RSV now.

Adding together the risks for YEL-AND and YEL-AVD for the older population comes to 3.4 cases per 100,000 vaccinations, or 0.0034%. As a comparison, risk of airplane crash is about 1 in 11 million (o.oooo1%) and risk of being struck by lightening is 1 in a million or less (0.0001%). Of course these risks vary by how many miles you spend on airplanes and how often you are out walking around in thunderstorms. Weighing my yellow fever vaccine risks and benefits, I chose to receive the vaccine rather than not travel to Ethiopia where my specific yellow fever risk was very low because I was staying at high altitude for most of the time.

Speaking of Travel

I timed my blog hiatus with a major trip to the Umbria region of Italy. It was a hiking vacation through rural areas with occasional forays into medieval towns and was a wonderful experience. I'm still nursing a few minor musculoskeletal aches and pains - my muscles and joints aren't what they used to be.

In addition to beautiful churches, ruins, and the medieval towns, I was also surprised to see many unfamiliar butterfly species including this Hipparchia hermione example.

Unless otherwise indicated, the content and opinions expressed on this web site are those of the author(s). They are not endorsed by and do not necessarily reflect the views of the George Washington University.
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