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Yes, I know this blog always deals with bugs, but this time I'm referring to the slightly larger bug forms. I think I saw my first Phoebis sennae in Maryland on Friday. My wife and I had taken advantage of the unusually delightful weather to make a dash to the West River in Maryland for some kayaking. I wasn't expecting to see a butterfly haven but happened on a flutter of butterflies right beside a public boat launch area.

First I guess I should mention the other creatures you expect to hear about in these pages, recognizing that viruses aren't considered life forms so maybe are not analogous to butterflies.

Pediatric Mpox

A new article nicely describes Mpox in the pediatric population. Multiple investigators from the WHO focused on the 1.3% of Mpox cases globally that occurred in individuals under 18 years of age. Only 1 ICU admission and 0 deaths were reported. Mode of acquisition below shows that contact with infected individuals and contaminated material predominated in younger children, while sexual encounters were most common in adolescents. Some of the analysis was limited by lack of complete data such as sexual history and, to a lesser extent, clinical findings. I don't think this study included US patients, but they have been reported separately a year ago.

Vaccination Against Disease X

No, this isn't something Elon Musk (he of the bizarre fascination with the 24th letter of the alphabet) came up with. Here, Disease X refers to unknown pathogens with the potential to cause pandemics. The University of Oxford just announced US$80 million in funding to continue research on the ChAdOx technology used for the Oxford - AstraZeneca covid vaccine marketed as Novavax in the US. This vaccine was associated with rare thromboembolic events and is no longer available in the US and UK. Let's hope future pandemic preparation continues to receive funding.

COVID Variant Hand-Wringing

I still see a lot of attention to covid variants, which is appropriate, but it must be tempered by the observation that the numbers are very low. Of course, any interpretation of these numbers must be made with the recognition that cases, hospitalizations, and even deaths are not being tracked in the same way as at the height of the pandemic and thus difficult to compare to prior numbers.

The BA.2.86 variant is a major focus in spite of its very small numbers. As I've mentioned before, this attention is due to the large number of mutations that could improve its ability to escape immunity from vaccines and prior infection. The latest CDC assessment again states that there is no evidence it causes more severe disease, and the main question is still immune escape and "fitness" qualities, i.e. how well it can outcompete other variants to become predominant.

The UK has a more detailed analysis (I think I'm becoming favorably biased towards the UK reports). Here's a timeline of the current 27 BA.2.86 cases identified worldwide so far. Note that for a BA.2.86 case to be identified, the infected individual would first need to undergo testing and then have that sample sequenced, so just the tip of the iceberg here.

BA.2.86 also has been seen in wastewater samples all over the world for some time. Here is an assessment from the UK: "...the variant is present in multiple countries on multiple continents, detected at a low prevalence amongst clinical cases or in wastewater. Although an increasing number of countries are reporting detection, there is as yet no clear signal of growth within any of these individual countries...No conclusions can be drawn about the fitness of the variant based on this data, and a full range of options – from less fit than other circulating variants, to a large jump in fitness – are still possible, given the available data."

As always, stay tuned.

Number Needed to Vaccinate for Covid Vaccine

To continue in my Anglophilic vein, the UK also provided a wonderful analysis of NNV. I copied one of their tables here (IS denotes immunosuppression):

The NNV reflects the number of individuals in those categories that would need to be vaccinated to prevent one additional hospitalization. The NNV is lower in the immunosuppressed and elderly populations. The estimates don't go below age 15; as you may be aware, vaccination of children in the UK is less of a priority than in the US, so it's hard to get NNV in young children in the UK.

In general, if one looks at covid vaccination at the individual level, at every age the benefit/risk ratio of the vaccine outweigh those of natural covid infection. From a population health perspective, the cost of vaccination to society increases when younger age groups are included in the analysis.

Vibrio vulnificus

CDC issued a health alert advisory this past week. If you are unfamiliar with severe infection related to V. vulnificus, please read this. Most notable and perhaps underemphasized in the lay press are the risk factors for severe, life-threatening disease: diabetes, immunocompromised states, and liver disease. Make sure your patients with these risk factors are aware of steps to avoid this infection and what to do if early signs develop. The infection can move very rapidly in these high-risk patients.

Vladimir and Me

I'm speaking of Nabokov, the writer. He is most known (and in some misguided circles, despised) for his novel Lolita, published in 1955 (1958 in the US). Fewer people are aware that he was an accomplished lepidopterist. The September 4 issue of the New Yorker reprinted a 1948 essay where he extolls the delight of butterflies and related creatures. Who knew that a mixture of molasses, beer, and rum applied to tree trunks attracts hungry moths at night? Read the essay if you have a chance, I think limited free access is available to non-subscribers. You'll experience some incredible writing, even if you aren't convinced to love butterflies and moths.

Phoebis sennae courtesy of the US Forest Service.

Living in the DC area, it's impossible to ignore the news on the looming debt ceiling deadline. Thankfully, we don't have a lot of infectious diseases causing immediate worry.

It's RSV Week

No, we haven't had any bizarre spring outbreak of RSV disease, just a spring outbreak of RSV news.

I wasn't able to view the FDA VRBPAC meeting about the Pfizer RSV vaccine for pregnant women, but I've gone over the documents, slides, and news reports. From a superficial view, the committee members voted unanimously that the vaccine, administered to pregnant people at 24-36 weeks gestation, was efficacious in preventing medically-attended lower respiratory tract infection (MA-LRTI) in their newborns from birth through 6 months of age. They also voted that the vaccine was safe, although 4 of the 14 panel members voted "No" for the safety issue.

Looking at the efficacy numbers, the vaccine efficacy was 57.1% (95% CI 14.7-79.8%) for RSV+ MA-LRTI and 81.8% (40.6-96.3%) for severe (defined as tachypnea, oxygen desaturation, need for high flow cannula or ventilatory support, ICU admission, or unresponsiveness) RSV+ MA-LRTI. The main trial involved about 7000 mothers, randomized equally to vaccine or placebo. As you can see, the confidence intervals are quite large, indicating the relatively low numbers of the outcomes of interest. Efficacy for severe disease dropped to 69.4% at 6 months of age, again with a wide confidence interval. The numbers are pretty good for a respiratory viral vaccine. Here's a screenshot of one of the FDA presentation slides for severe disease:

For safety evaluation, both mothers and infants were studied. The main concern that arose had to do with a higher rate of premature delivery in the vaccine group. Here's the safety summary from the FDA presentation:

You can see that the premature births/deliveries percentages are close to one another, and the differences did not reach statistical significance. Still, it is notable if in fact there is some causal association - remember, it would be a vaccine potentially given to all pregnant people. Also, it's a bit more concerning because over a year ago GlaxoSmithKline paused their trials of a maternal RSV vaccine over safety concerns. The safety concern with the Pfizer vaccine would likely require tens of thousands of participants in new clinical trials to have enough power to see if the relationship holds; rather, this would be something to focus on with post-marketing surveillance if the vaccine is approved.

At the time I write this, FDA has not yet issued an approval statement for the vaccine. Of course, we have plenty of time since the next RSV season is likely months away. Also, we must remember there is another potential new alternative for RSV severity mitigation in young infants, the long-acting antibody preparation nirsevimab. The CDC's ACIP will discuss maternal/pediatric RSV prevention at their meeting on June 22. It may be that nirsevimab is a better choice than vaccine at this point. I'll be very interested to follow that June ACIP meeting.

But Wait, More RSV

A couple new studies appeared last week. One longitudinal cohort study in Tennessee demonstrated an association between lack of RSV infection in the first year of life and lower risk of asthma developing within a 5-year followup. This isn't the first study revealing that early RSV infection can lead to subsequent asthma diagnosis. The study involved only term infants, suggesting significant potential benefit of RSV preventive measures beyond just premature infants.

Another study from Colorado reported that lack of exposure to RSV during the bulk of the covid pandemic could be the reason we saw such a severe RSV season this past fall and winter. We'll need to see the results replicated in other locales, but the study was well done and the mechanism is biologically plausible.

Covid News

Not much has changed in the past week, but a few items of interest appeared. First, the World Health Organization has recommended the next iteration of vaccine be a monovalent product targeting the XBB lineage, abandoning any inclusion of the ancestral strain. I'll be interested to see if the US follows suit when FDA meets June 15 to discuss composition.

A recent modeling study also caught my attention. As I've said before, modeling studies have many assumptions and can end up being totally off base, but this one from multiple institutions shows that, if we had done a better job with covid booster vaccinations in fall of 2022, we would have seen a significant decrease in both hospitalizations and school absenteeism in the pediatric population last winter. Perhaps I'm cherry-picking this study because it agrees with my bias that covid vaccination benefits all age groups, but the study methodology seems sound given the limitations of any modeling study.

Lurking in the Shadows

Mpox remains a problem, particularly for men who have sex with men. The vaccine is highly effective.

Influenza H5N1 continues to lurk, causing sporadic infection primarily among those with very close contact with fowl including chickens. The US Department of Agriculture is studying a vaccine for poultry as well as use of other mitigation strategies.

CDC has some new guidance on building ventilation, maybe one of the lessons learned from the pandemic that would be useful to implement now in your office and/or home, depending on need and available financing.

I'll keep my eye on all these shadows, but in the meantime I'm turning my attention to a more practical matter of my carport's battle with carpenter bees. Listen to the soundtrack in the link, it sounds like it came from a bad horror film.