Quite an eventful week! In general, I try to keep politics out of my commentary, though I fell short of this goal in my February 25, 2024, post where I blasted the Surgeon General of Florida; that may be the only time I've singled out an individual in a negative manner in this blog. Now, I find that his name is being mentioned as the next Secretary of Health and Human Services. All of this reminded me of an almost 300-year-old pamphlet.
But first a bit of the other health news from last week.
Mayaro Virus
In spite of my voracious appetite for medical knowledge, the list of viruses I've never heard of is lengthy. Now my list is one item shorter due to a new report. Mayaro virus is another of the arthropod-transmitted alphaviruses prevalent in parts of South America, causing a febrile illness with severe arthralgias very similar to its cousin Chikungunya virus. Primates serve as a reservoir with the primary vector the mosquito Haemagogus janthinomys. If like me you are a bit shaky on some elements of South American geography and history, Suriname is a former Dutch colony located just north of Brazil and has territorial disputes (in light green) with neighboring countries.
Measles in Vietnam
Vietnam is introducing earlier measles vaccines to try to stem an epidemic. In this WHO Western Pacific region report, you can see Vietnam is going the wrong way in measles incidence. Like the rest of the world, we all "enjoyed" a pandemic period where many traditional infectious diseases transmitted by respiratory routes showed significant declines due to non-pharmaceutical interventions, only to now reappear in greater numbers. For measles, Vietnam showed an incidence of 7.4/million population in 2020, dropping to 0.3 in 2022 but now back up to 7.1/million in 2024.
Normally Vietnam recommends measles immunization at 9 months of age, but now this is being dropped to 6 months due to an increase in cases in younger age groups. (You'll need Google translate for this link.)
Computerized Radiograph Interpretation for TB?
Although this study was performed only in adults, I thought it was worth mentioning as a possible glimpse of the future. Investigators in Africa and southeast Asia looked at the performance of a computer program to interpret chest radiographs in about 1400 adults with cough > 2 weeks in duration and found the program to have significantly higher sensitivity than a relatively new blood test for host response gene activation in TB as well as superior to CRP. When trying to diagnose TB in resource-poor settings that may not have access to good molecular and other microbiologic methods for TB diagnosis, we need every tool available. I'll be interested to see how newer methods for TB diagnosis evolve.
More on Bird Flu
CDC reported that 7% of 115 dairy workers at farms known to have infected cows showed serologic evidence of influenza A H5N1 infection. Four of the 8 seropositive workers did not recall having any respiratory signs or symptoms since the cows were first noted to be sick. This rate wasn't terribly different from the 60% of those with no illness history in the seronegative group. Given that H5N1 so far seems to be a mild illness in humans, the finding of asymptomatic infection isn't surprising. Clearly we need a lot more data on human illness in these and other settings.
Benefits of Quadrivalent Meningococcal Vaccine
Of our recommended vaccines, meningococcal vaccine probably has the lowest "return on investment." Meningococcal disease is relatively rare but comes with very high morbidity and mortality when it does occur. This modeling study estimated the number of cases of invasive meningococcal disease in 11-23 year-olds prevented by vaccination during the period 2005-2021. One always needs to take modeling studies with a grain of salt because they by necessity make a lot of assumptions. The authors did a good job of trying to look at all possibilities. They concluded that "vaccination averted an estimated 16 (95% CrI, 8-31) deaths among adolescents aged 11 to 15 years and 38 (95% CrI, 19-75) deaths among those aged 16 to 23 years." I guess those are small numbers when compared to the entire US population, but this is still a meaningful benefit.
WRIS
Things are still relatively quiet, though with regional variations.
I did happen to note that wastewater levels of RSV are very high in Maryland, so maybe that will be the first pathogen to increase in my region.
Make America Healthy Again
I feel like the MAHA acronym was one of the nicer-sounding political slogans to appear recently. However, the fact that it was popularized by a notorious pseudo-science fringer concerns me for what might lie behind MAHA. That made me recall a short treatise by Jonathan Swift (of Gulliver's Travels fame) that I came across a long time ago. I read it again a few times this week, and this highly satirical essay entitled "A Modest Proposal" is worth 10 or 15 minutes of your time. I think it is best read without knowing where the narrator is going, so I'll give you a SPOILER ALERT. You can read the original document in the link now, before reading what I write below, or you can just forego the surprise and keep on with my take below.
The narrator beings with an "objective" view of the problem, in 18th century Ireland, of the economic woes of a large section of the populace. He particularly hones in on the difficulties that parents in lower economic strata have in providing for their children. After going through some numbers assumptions that we can only guess at the accuracy, he decides that Ireland has about 120,000 children born to impoverished parents annually. How can the country solve this problem? He offers his modest proposal, or "humble solution:" It's a sudden turn in tone, to say the least.
"I have been assured by a very knowing American of my acquaintance in London, that a young healthy child well nursed, is, at a year old, a most delicious nourishing and wholesome food, whether stewed, roasted, baked, or boiled; and I make no doubt that it will equally serve in a fricasee, or a ragoust."
Yes, Mr. Swift in his satirical essay is proposing cannibalism as a solution to poor families trying to raise their children. He goes on to describe various details of preparation and serving.
MAHA sounds OK now, but I fear of this becoming another modest proposal. I'll withhold my judgment until we see more details of the plan.
We've had a slow week of infectious diseases events, but that hasn't slowed down the chatter and noise. I've tried to distill out the more important topics this week.
The Covid Front
Even though US tracking systems have been greatly dismantled in many states, I can still safely say we are in a lull. Naturally, thoughts turn to predicting the next surge and how to mitigate it.
I mentioned in my May 5 post that the FDA's Vaccines and Related Biological Products Advisory Committee meeting to decide on composition of the next iteration of covid vaccine would be held on May 16 and likely would make the same decision as the WHO already has, using the JN.1 variant. However, they suddenly postponed this meeting to June 5. FDA didn't offer an explanation for the postponement, but the last-minute change leads me to suspect that they wanted a little more time to think about newer variants with possible significant differences in immune-escape properties. Here's a deeper dive into that.
As you can see in this latest CDC variant report, the dark purple JN.1 proportion is decreasing, with KP.1 and KP.2 starting to expand. Both of those are in the JN. 1 lineage:
All of the JN and KP variants are informally called FLiRT variants, an easier shorthand than trying to remember all the letters and numbers. It stands for amino acid substitutions, in this case phenylalanine (F) substituted for leucine (L) in the 456 position (F456L) and arginine (R) to threonine (T) in the 346 position (R346T) in the spike protein genomic code. These 2 mutations are in antibody binding sites that neutralize the virus, and the mutations make SARS-CoV-2 less vulnerable to vaccine- and infection-acquired antibodies. A JN.1-derived vaccine likely would offer some protection, but perhaps by the June meeting we'll know a bit more about all of this. If they do recommend using KP.2 instead of JN.1 for example, I don't think there would be a significant delay in mRNA vaccine production by Pfizer and Moderna, but it might cause problems for other vaccine platforms such as the one used by Novavax, the other approved vaccine in the US which is an adjuvanted protein subunit vaccine. I'll be watching as much of the June 5 meeting as I can.
HPAI
Now we have a grand total of 2 people in the US infected this year with Highly Pathogenic Avian Influenza, along with a lot of cattle and other animals; a recent MMWR provides details. The new, improved CDC website has lots of helpful links. The second case, in Michigan, was similar to the first human case of A H5N1 infection in Texas - very mild illness with conjunctivitis as the primary symptom. This strikes me as very unusual for evolving epidemics in that usually the more severe cases are identified first because they are more likely to come to medical attention. Both of these cases were identified through surveillance of dairy workers which suggests to me that currently HPAI in humans is a very mild infection, possibly with high rates of asymptomatic infection. This is a good thing generally, but also problematic for tracking infection rates. The MMWR reports only 350 exposed dairy workers are being followed, a very small number. Ideally we'd have more tracking of cattle and dairy workers, regardless of illness or exposure to infected animals. Getting cooperation from dairy farms will be difficult, we're talking about livelihoods in an industry where a shutdown for a cow outbreak could send someone into bankruptcy.
I'm watching multiple feeds to keep up with all of this. A report in NEJM last week was encouraging - heat inactivation of spiked milk samples significantly lowered infectivity in mice fed the milk.
Also in the good news department, USDA reported preliminary findings on HPAI detection in muscle tissue of culled dairy cows. 95 of 96 samples tested so far were negative by PCR. Note that these were condemned animals, none of the meat entered the food supply.
On the somewhat negative side, more cattle herds have been hit with the virus, according to USDA.
Poultry outbreaks also continue with Minnesota registering more detections last week. Note that backyard flocks are not immune to HPAI.
On a slightly related topic, I was disappointed but not surprised to learn that the World Health Assembly, the decision body for the WHO, removed a pandemic preparedness treaty that was to be discussed at their meeting starting May 27. It appears that political considerations caused the cancellation; much misinformation is circulating, especially in the US. The treaty would help countries design programs for pandemic preparedness and in no way allows the WHO to control countries' own public health programs as claimed by some sources.
Potpourri
A scattering of reports might be interesting for readers. First, beware of undercooked bear meat. Six out of eight people who consumed undercooked, previously frozen black bear meat developed trichinellosis. Freezing doesn't kill Trichinella parasites. Beware the (undercooked) bear.
CDC released a Health Advisory Network alert for meningococcal disease in Saudi Arabia, although this is pretty much routine for this time of year during religious pilgrimage season. Travelers to the region should be immunized for meningococcal disease, which is more easily transmitted in the crowded situations during Islamic pilgrimages to Mecca.
Speaking of Noise
I'm pretty sure I've never mentioned this in the blog, probably because I'm so embarrassed, but I'm a 2-time harmonica school dropout. This last exit was due to a combination of my inability to master bending notes on the diatonic harmonica and the fact that my dog runs away from me every time when she hears my mellifluous tones. I've now solved the second problem by clearing a practice space in my trash-heap of a basement where the dog can't hear me, but bending will still be a challenge. It's a technique to hit notes that are in between standard notes; there are maybe hundreds of online instruction sites for how to form your mouth to do this, but basically it's just trial and error and takes several months for most people.
Maybe by announcing my intentions I'll be shamed into pulling it together this time and can return to harmonica school. I can't promise to report on my progress, especially if I have none!
It was a busy week for infectious diseases, not in the sense of more outbreaks but rather more epidemiologic and vaccine data that point to better health for the future.
The big topic of the week was the Advisory Council on Immunization Practices regular February 2-day meeting. In retrospect, pediatric healthcare providers won't have any major new recommendations to work with; those are likely coming following the next meeting the end of June. I wasn't able to view as much of the meeting as I had hoped, patient care interfered a bit, but I did review all the presentations for those that I missed hearing live. Let's dive in.
ACIP
The Council discussed 9 different topics, but only 3 involved voting: COVID-19 vaccines (vote in favor of a spring vaccine for some high-risk people), Chikungunya vaccine (vote for use in some US adult travelers and in laboratory workers), Td vaccine availability for those with contraindications to receiving pertussis vaccine (discussion followed by a vote regarding the Vaccines for Children progam), influenza vaccines, polio vaccines, RSV vaccines for adults, meningococcal vaccines, pneumococcal vaccines, and the new Vaxelis combined product for diphtheria, tetanus, pertussis, polio, Hib, and hepatitis B. I'll expand on just a few of these topics. (Note all of the graphs/figures below are from the ACIP web site presentation slide link for the February meeting.)
RSV
We saw the most up-to-date representation of RSV epidemiology, showing that the epidemic curve for this year looks a lot like prepandemic years (see last presentation in RSV session).
A good part of the discussion centered on risk of Guillain-Barre syndrome following vaccine, compared to risks of GBS in the baseline population. Both are rare events, but I think at this point it is reasonable to conclude that GBS is a rare risk of RSV vaccination, though not enough to outweigh benefits for high risk populations.
A quick look at the benefits versus GBS risks for adults > 60 years of age (Melgar presentation from RSV session):
Note risks might vary with vaccine type - hard to know with rare events and large confidence intervals, plus both in the ballpark of background GBS numbers.
Influenza
This session was interesting for me to see a preliminary assessment of vaccine effectiveness for the 2023-2024 flu season. I'll just show you an overview of VE in the pediatric population; note that multiple methodologies are used to measure VE. (See slides from Frutos presentation in the influenza section.)
This is good VE for flu, certainly the CDC and WHO were on track for choosing the best combination of strains for this season. Look for the vote for next season's vaccine composition in June.
Meningococcal Vaccines
The focus of the discussion was how best to incorporate meningococcal B vaccine now that we have an approved combination vaccine containing this serogroup. Here are the main options discussed, from the 1st Schillie presentation:
The issues are complex, primarily due to 3 factors. First, meningococcal group B infections are extremely rare; traditional cost-effectiveness models show that meningococcal B vaccination in the US is by far the most expensive vaccine; very few cases are prevented due to the rarity of infection. Second, vaccination at age 11-12 risks significant waning of immunity by the age for peak meningococcal disease in adolescents; it might make sense to move the first dose to a later age. (The main argument against this is the confusion caused by eliminating the long-standing practice for vaccination at age 11-12, perhaps lowering overall vaccine acceptance.) Third, it is clear that not all meningococcal disease risk in adolescents is equal: college attendance is prime, but there are other behavioral risk factors (1st Schillie presentation):
The discussion was mainly to hear input from all stakeholders and then go back to the drawing board. Expect a vote on this at the June meeting - it will greatly impact your summer vaccine guidance for adolescents and young adults.
COVID Vacines
This section of the meetings seemed to garner the most publicity. Of course most of the results presented dealt with adults, given the relatively lower risk for bad outcomes in children plus low rates of vaccinations. Most helpful I thought were the discussions about covid VE in recent months looking at the fall monovalent vaccine.
These are great numbers. Also mentioned was the fact that waning of efficacy hasn't been seen yet, but that could just be a result of not having enough time to pass since the fall vaccine. Other good news is that in vitro studies suggest that the current monovalent vaccine is likely to protect against newer variants.
Special situation for people ages 65 years and older: People ages 65 years and older should receive 1 additional dose of any updated (2023–2024 Formula) COVID-19 vaccine (i.e., Moderna, Novavax, Pfizer-BioNTech) at least 4 months following the previous dose of updated (2023–2024 Formula) COVID-19 vaccine. For initial vaccination with Novavax COVID-19 Vaccine, the 2-dose series should be completed before administration of the additional dose.
That "should" wording was the subject of much debate, finally choosing this wording more for simplicity of recommendations. The gnashing of teeth came about for a good reason - people in the lower end of this age population who do not have underlying risk factors will have less benefit from a spring vaccine because rates of bad outcomes in the post-pandemic period are lower.
Recommendations for younger people with moderate or severe immunocompromise have slightly different wording:
People ages 12–64 years who are moderately or severely immunocompromised may receive 1 additional dose of any updated (2023–2024 Formula) COVID-19 vaccine (i.e., Moderna, Novavax, Pfizer-BioNTech) at least 2 months after the last dose of updated (2023–2024 Formula) COVID-19 vaccine indicated in Table 2. Further additional doses may be administered, informed by the clinical judgement of a healthcare provider and personal preference and circumstances. Any further additional doses should be administered at least 2 months after the last updated (2023–2024 Formula) COVID-19 vaccine dose.
People ages 65 years and older who are moderately or severely immunocompromised should receive 1 additional dose of any updated (2023–2024 Formula) COVID-19 vaccine (i.e., Moderna, Novavax, Pfizer-BioNTech) at least 2 months after the last dose of updated (2023–2024 Formula) vaccine indicated in Table 2. Further additional doses may be administered, informed by the clinical judgement of a healthcare provider and personal preference and circumstances. Any further additional doses should be administered at least 2 months after the last updated (2023–2024 Formula) COVID-19 vaccine dose.
For all age groups, the dosage for the additional doses is as follows: Moderna, 0.5 mL/50 ug; Novavax, 0.5 mL/5 ug rS protein and 50 ug Matrix-M adjuvant; Pfizer-BioNTech, 0.3 mL/30 ug.
As an aside and not receiving much media attention, a new report showed that vaccine mandates didn't help and probably hurt. States with vaccine mandates didn't have higher covid vaccination rates and actually had lower covid booster uptake and flu vaccination rates. Yikes!
Nipah Virus
Never heard of it, or hard-pressed to find facts at the tip of your tongue? Most providers in the US don't need to know much about this bat-borne virus, but if you have any patients planning a trip to Bangladesh you may want to advise them not to consume raw date palm sap (not on my list of delicacies so far) and to stay away from pigs.
NiV gets its name from the village of Sugai Nipah in Malaysia, site of a 1999 outbreak highlighted by cases of encephalitis in pig farmers. Outbreaks typically occur in Bangladesh and India. Now, the World Health Organization reports that 2 individuals, including a 3-year-old girl, have died from the infection after consuming raw date palm sap. The sap likely was contaminated with fruit bat droppings laced with NiV. In addition to signs and symptoms of encephalitis, typical findings are those of nonspecific febrile illness. Diagnosis is difficult until/unless encephalitis findings appear. It's a relatively uncommon infection even in Bangladesh, but mortality is high.
Good Attitudes
It's a sign of our times that I was pleasantly surprised to see a vaccine attitude survey with good news. Investigators from RAND corporation, University of Iowa, and CDC performed an online survey of 1351 parents to assess their willingness to have their children 5-18 years of age receive a vaccine to prevent Lyme disease. About two-thirds of parents definitely or probably would vaccinate their children. The boldface numbers below show statistically significant predictors of willingness to have their children receive Lyme vaccine, with willingness of the parent to receive the vaccine the strongest predictor.
In case you were wondering, for the purposes of this survey the high incidence states were Connecticut, Delaware, Maine, Maryland, Massachusetts, Minnesota, New Hampshire, New Jersey, New York, Pennsylvania, Rhode Island, Vermont, Virginia, Washington D.C. (yes, I don't need to be reminded it's not a state), West Virginia, and Wisconsin. They also looked at states characterized as "emerging" Lyme disease states (Iowa, Ohio, Illinois, Indiana, Michigan, North Carolina), but this group had a slightly lower rate of willingness than in high incidence states. Lyme vaccine trials in the pediatric and adult populations are ongoing, so don't be surprised if parents and children have this option in the next year or so.
Speaking of attitudes, take a look at AAP's new guidance for improving vaccine communication and uptake. It has an excellent literature review and describes various strategies that pediatric healthcare providers can use to improve vaccine acceptance. It is still true that different studies sometimes have reported different conclusions on how best to discuss vaccine hesitancy with parents, likely because it is very difficult to design studies that deal with such subjective issues in a uniform manner.
WRIS
Winter respiratory infection season is still chugging along, mostly due to influenza which is stubbornly persisting in scattered areas in the US. What a crazy patchwork!
New Covid Isolation Guidelines
Maybe this has overshadowed everything in the news. I've discussed this recently in the blog and was expecting the new guidelines to come in April, but CDC bumped it up by a month. It incorporates new information about covid epidemiology, hospitalization rates, and outcomes with balancing for impacts on the economy and on school and work attendance into a comprehensive guideline for all respiratory infections. So, no longer do we have a specific number of days after covid diagnosis to remain out of school or work. The document has multiple links and is pretty complicated. The CDC's press release is a good summary, however. Note that vaccination is still stressed heavily, though I expect it will be ignored by the same hardcore group of antivaxxers. Here's the quick blurb:
"When people get sick with a respiratory virus, the updated guidance recommends that they stay home and away from others. For people with COVID-19 and influenza, treatment is available and can lessen symptoms and lower the risk of severe illness. The recommendations suggest returning to normal activities when, for at least 24 hours, symptoms are improving overall, and if a fever was present, it has been gone without use of a fever-reducing medication."
I am very much in favor of these new recommendations. Circumstances have changed, and we have learned a lot from management of the pandemic these past few years. I just hope our vaccination rate will improve and that people with any respiratory symptoms at all will be aware that they can pose a significant risk to others who may have circumstances putting them at high risk for hospitalization or death from respiratory viruses. Also, please note this only applies to community settings; there are no changes for healthcare settings.
Squirrel Redux
If I were superstitious, I wouldn't mention the fact that my neighborhood squirrels still have not attacked my newly-positioned bird feeder. I was bemused by an article in the Local Living section of the Washington Post last Thursday, clearly written by a squirrel lover. Squirrels do have value, and I have no desire to wipe them off the face of the earth. I just don't want them eating all my bird seed.
A friend of mine in South Carolina with an array of bird feeders and birds also has come to terms with squirrels, albeit somewhat differently than my crazy solution. He just monitors things, and when the squirrels reach a point that he feels they become a significant barrier to maintaining bird happiness and seed access, he uses a humane trap to collect squirrels and then release them far from his neighborhood. I won't disclose where he releases them, but it sounded like a good place for squirrels and unlikely to bother too many people. I wonder if any of them found their way back to him.
I'm only mildly ashamed to admit that when I saw a recent publication of a randomized controlled trial of symbiotic therapy for post-acute COVID-19 syndrome (PACS), I had no idea what the term meant. Now I know more, and the study brings up some intriguing thoughts but no direct answers.
First, let's talk about a couple other issues.
Winter Respiratory Illness Season
I'm inventing a new acronym, WRIS, just because I can. CDC went so far as to issue a Health Alert Network posting reminding all of us about the low vaccination rates for covid, influenza, and RSV as well as the availability of treatments for the first 2 infections. So far, flu vaccine coverage in the pediatric age range (6 months to 17 years) is about 36%, pretty poor. The post has a lot of good information throughout, but if you're pressed for time please at least take a look at Table 2 with its links for suggestions for discussions with the unimmunized.
Looking at CDC's weekly viral report page, respiratory illnesses continue to increase. Nationally, emergency department visits for WRIS continue to rise, driven largely by influenza. RSV may be past its peak.
Lastly, covid is till out there with high levels in wastewater suggesting we'll see a bigger bump in illness soon.
Although I've presented the national picture, be aware that many of these sites have the ability to display findings by state and other jurisdictions, so you can see what's going on in your area.
Is Pediatric Omicron Infection More Contagious Than We Thought?
That's certainly the implication of a recent study looking at duration of viral shedding in infected children over a 90-day period in early 2022. It's important to note that the study looked only at duration of positivity of PCR at high levels thought to link to infectivity, and also at rapid antigen test (RAT) positivity over time. So, it wasn't a direct measure of whether these children actually transmitted infection at home or in school. With this caveat in mind, they found that 25% of children still had presumed infectious viral loads by day 7 of illness, a bit longer than guidelines recommend for isolation. RAT positivity was a mixed bag as usual (the watermark in the graph just denotes "accepted manuscript" as this paper was published for early online access).
This article shouldn't change practice per se. Looking back at publications of covid spread from children, the results are highly variable with some studies suggesting children have little role in spread. With this much variation in study results, likely the issue is multifactorial, making it difficult to come to any broad generalizations that apply across ages, settings, and time.
Meningococcal B Vaccine and Shared Clinical Decision Making
A few weeks ago I mentioned that healthcare providers don't have enough information at their fingertips to allow parents and patients to truly participate in decisions about vaccination. A new publication about meningococcal serogroup B disease rates helps inform the discussion for meningococcal B vaccine. As you may recall, the ACIP and AAP recently updated meningococcal B vaccination information with the approval of a new pentavalent vaccine. Meningococcal B disease in the US is relatively rare, making risks pretty low overall regardless of vaccination status.
The authors looked at rates of meningococcal disease in persons 18-24 years of age in the years 2014-2017, so not altered by any pandemic considerations. They found 229 confirmed or probable meningococcal disease reports, for an overall rate of 0.18 per 100,000 person years. 120 of the 226 cases for which they had college status were undergraduates, the group at highest risk of meningococcal B infection in the US and the main target for any vaccine intervention. Of those 120 students, 89 had infection with serogroup B.
Students attending 2-year colleges did not have an increased risk of infection compared to non-college students. Only 4-year college attendees had increased risk, and the risk was higher among first-year students and among "Greek life" participants, probably because those groups have a bit more crowding and sharing of beverages, etc.
The authors had some excellent advice in their discussion:
"These findings might be useful for patients, parents, and clinicians when discussing whether to vaccinate adolescents against serogroup B before they go to college. Adolescents planning to live on campus at a 4-year college, particularly ones planning to engage in Greek life or attend schools known for their social life, may benefit more from vaccination. Immunity from MenB vaccines is known to wane quickly, but concentration of risk among first year college students means there is an opportunity to prevent relatively more disease by vaccinating students shortly before they go to college so that the timing of maximum protection overlaps with the highest period of risk."
"Requiring or recommending vaccination against serogroup B disease might not be a tenable policy decision for all colleges, but our findings suggest that 4-year colleges with large numbers of students participating in Greek life or with a high party school ranking might be most likely to benefit from such policies, as these schools were significantly more likely to experience serogroup B cases or outbreaks."
Did you catch that party school mention? Another aid for parents referenced in the study was a ranking of party schools. Those with high rankings presumably represent higher risk for meningococcal B disease. No surprise to me, my undergraduate school didn't make the list.
What I really wanted to know was the Number Needed to Vaccinate (NNV), i.e. how many students would need to be vaccinated to prevent 1 additional case of meningococcal B disease. I knew it would be high because this is such a rare event. It took a little work because I needed a denominator - I knew the number of cases, but I didn't know how many were in the risk group. I had to go to a supplementary table in the article, then look at web links to try to choose a reasonable denominator. I settled on the number of full-time students in undergraduate schools in 2017; it included both 2-year and 4-year colleges. That number, from the National Center for Education Statistics, was 12,085,000. Let's assume the MenB vaccines are 100% effective (they are not, but all are pretty close and I got tired of calculations) and that none of those 89 students in the study were vaccinated (the authors couldn't determine precisely the vaccination rates in their study). NNV is the reciprocal of the absolute risk reduction, which is the rate of infection in the control group (89/12,085,000) minus the rate in the experimental (vaccine) group, which we are assuming to be zero. Crunching those numbers gives us an NNV of 135,786. That is to say, we would need to vaccinate that number of students entering full-time college with a meningococcal B vaccine to prevent 1 additional infection. That NNV number is astronomical and orders of magnitude above NNV for other recommended vaccines. If we were doing a cost-benefit analysis of meningococcal B vaccine, it wouldn't jive at all, but what isn't taken into account is the panic that develops when a case of meningococcal disease occurs on a college campus. Also, I made a lot of assumptions in coming to that number, so it's really just a very rough ballpark. Any decision would need to balance vaccine risks (virtually zero; anaphylaxis from vaccination found 33 cases in 25,173,965 vaccination events in one study, a similar ballpark to the rate of meningococcal B disease above.) This all goes to show that using absolute risk reduction can be more informative than looking at relative risks, which are ratios. For example, in the meningococcal B rates study, participation in Greek life carried a 9.8-fold increase in infection risk compared to other students - a high number that doesn't convey the extremely low infection rates. News stories invariably talk about relative risks rather than absolute risks - bigger numbers sell more papers/advertisements.
So, you can see why those quoted discussion points from the authors are so important. If a parent/potential college student asked me about meningococcal B vaccine, I'd start with saying meningococcal disease is very rare but also very dangerous, with a high fatality rate if one is infected. The risk of getting the infection is very low, about equal to risk of having a life-threatening allergic reaction to any vaccine, both being very rare. [The provider could insert in here if they've ever seen in case of anaphylaxis with a vaccine.] If the plan is to attend a 4-year college, live in a dormitory or fraternity/sorority, and have an active "party" life, the risks for infection are higher though still rare. Some people might value having some more piece of mind and choose to receive vaccination; others may not. Regardless, if at school one hears that you have been exposed to someone with meningococcal infection, you need to follow specific guidance from the local health department or student health team without delay - antibiotic and/or vaccination might be life-saving.
What I Learned About Synbiotics
I'm exhausted after too much number crunching, let's look at a new study that certainly is food (pun intended) for thought. A few definitions first:
Prebiotic - a nondigestible food ingredient that promotes the growth of beneficial microorganisms in the gut
Probiotic - live microorganisms ingested to improve the gut microbiome
Synbiotic - a combination of prebiotic and probiotic substances
The randomized, double-blind, placebo-controlled study looked at 463 adult patients in Hong Kong who were previously diagnosed with covid and fulfilled a standard definition of PACS. The experimental group received twice daily oral doses ("sachets") consisting of 3 probiotic bacteria and 3 prebiotic compounds; the control group received vitamin C with inert additives such that the packets of oral doses were identical in appearance, smell, and weight. The choice of synbiotic elements was based specifically on prior Hong Kong microbiome studies that suggested beneficial elements. The main outcome of interest was change in PACS symptoms at 6 months.
Although there was no difference in quality of life or physical activity between the 2 groups, the treatment did seem to have a beneficial effect on several symptoms and was correlated with favorable microbiome changes.
Maybe some progress, we'll need to see more studies on synbiotic therapy for long covid, hopefully expanded to many different populations. I think I'll go get some yogurt for lunch.
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.
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."
