vaccine – Pediatric Infection Connection

Yellow Jack in the US? Are You Kidding Me?

Bud WiedermannOctober 22, 2023October 22, 2023Leave a comment

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.

Adventures in My Rabbit Hole

Bud WiedermannJanuary 15, 2023January 15, 2023Leave a comment

By my rough estimate, I've been in my private rabbit hole of infectious diseases and microbiology for over 50 years. Certainly covid has prolonged my stay. This past week I saw a number of new publications that are worth mentioning, I'll try to be succinct!

Tripledemic Tracking

After pausing for data entry to somewhat catch up after the holiday lull, let's look at the landscape.

Influenza

According to FLUVIEW, the country as a whole is seeing continued decline in flu cases. Remember I'm showing you just the hospitalizations confirmed to be flu, as a most accurate tally. Note that the dashed line is to call attention to the lag in reporting the past few weeks. Let's hope we don't see a rebound.

COVID-19

Percent positivity continues to rise, but a little tougher to determine accurate infection rates given all the nuances we've discussed recently.

The XBB.1.5 variant continues to hold the lion's share of the variant proportion in the US. I was interested to see that, at least so far, this variant is not a big deal in the U K. I expect that to change.

RSV

RSV-NET shows a continued decline in RSV infections, with the caveat that we might still be experiencing delayed reporting from the holidays. I don't expect RSV to trouble us any more this winter.

More on Long Covid

A new analysis from Israel suggests that most symptoms of long covid tend to resolve at 1 year follow-up for those individuals who had mild covid illness originally. This is an analysis from a large database which can have its own misleading reporting issues, but in the past this same database has had a good track record for being correct.

Bivalent Covid Vaccine Boosters No Better Than Monovalent?

Two small studies (here and here) in last week's NEJM suggest this is the case, from comparisons of antibody responses. I first commented on these studies last October when they were only in preprint form. Note these studies did not include children, so we could see some different results when those analyses are performed. The accompanying editorial by Paul Offit is a good read. It is essentially an "I told you so" discussion. Some may recall that he was the only member of the FDA VRBPAC panel last summer who voted against moving forward with the bivalent boosters. His main argument was that we didn't know if they were any better than monovalent boosters against the emerging variants, and these small studies appear to confirm his suspicions.

Please be aware this doesn't mean that bivalent boosters are worse, just that they may be no better than boosting with the monovalent vaccine, at least for now. Stay tuned for what should be a very stimulating discussion of future vaccine plans at the next FDA VRBPAC meeting on January 26.

A Clue to Myocarditis Mechanism Following Covid Vaccine?

Researchers in Boston reported results from 61 adolescents and young adults (16 who developed myocarditis and 45 who did not) who had received either the Pfizer or Moderna mRNA vaccines. They found an association of circulating spike protein in blood samples with the myocarditis group. They also looked at immune and cytokine patterns in the subjects. The discussion portion of the article brings up many possible explanations for how intact spike protein might be involved in the pathogenesis of myocarditis, but this is all very preliminary. Now we need more studies to confirm this association and further explore the immunologic phenomena accompanying it.

Note that nothing in this study changes the bottom line for vaccine advice: benefits of covid vaccination outweigh risks when we are considering myocarditis or any other endpoint for COVID-19.

Everything Old is New Again

No one seems to know definitely who first coined this phrase, but I mention it here to remind all healthcare providers to be on the lookout for those "old" vaccine-preventable diseases such as measles, mumps, rubella, and even diphtheria. This week the CDC gave us figures for vaccination rates in kindergarteners during the 2021-22 school year: not encouraging, but also not surprising. Another publication provided some some explanation for why we see problems with mumps outbreaks even in fully vaccinated adolescents and young adults. (Spoiler alert, it is waning immunity.) If any healthcare provider is a little fuzzy on diagnosis and management of these diseases, please review!

Speaking of old, I found that Alice's Adventures in Wonderland was published in 1865, and Down the Rabbit-Hole is the title of the first chapter. Maybe I'll reread it one of these years.

History Repeats Itself 2

Bud WiedermannJuly 18, 20212 Comments

The "Pandemic of the Unvaccinated"

Dr. Walensky's sound bite this past week quickly became the standard catch phrase in the media, and it isn't misleading. Our current COVID-19 infection rate is in the same (but slightly lower) ballpark as last summer, but what isn't in the same ballpark are numbers of hospitalizations, ICU admissions, and deaths, at least not yet. The main difference between this summer and last is the target population: now we are seeing the pandemic being driven by younger (unvaccinated) individuals who are less at risk for the more severe outcomes of COVID-19 infections. Clearly vaccines work, and we now have real-world evidence that demonstrates this. We are still in a race between variants and reaching herd immunity, and each one of those newly-infected individuals might be the one to develop and spread a more troublesome variant that not only has increased infectivity but also increased severity and/or ability to evade vaccine protection.

As a slight aside, yesterday (July 17) I tuned into a regular CDC/IDSA COVID-19 Clinician Call, and this one I thought was particularly useful with explanation of immunity from natural infection versus vaccines and a summary of COVID-19 antibody testing. The key take-home for antibody testing is that it should not be used to infer immunity following vaccination. These tests were only designed to predict likelihood that an individual was previously infected and says nothing about degree of protection. Just say no if a patient requests an antibody test to determine if they are immune. The recording from the July 17 session should be available within a few days.

Ready for Monkey Pox?

Also in the category of history repeating itself, we learned this past week about an individual with monkey pox in Texas, likely picked up in Nigeria. We see sporadic cases of monkey pox in the US, it isn't unexpected. Do you know what to look for to spot a case?

First of all, in spite of the name, don't ask about monkey exposure. Most humans acquire monkey pox from other animal reservoirs, principally rodents, in endemic areas. These areas include Central and West Africa. It can be a difficult diagnosis before the rash appears; the prodrome is nonspecific and consists of fever, malaise, headache, and myalgias. After the 1-3 day prodrome, the rash appears initially as macules and then progresses to papules, vesicles, and pustules. It is very similar to smallpox in that lesions tend to distribute more peripherally. Transmission from infected individuals to other humans most commonly is via droplet spread and likely requires prolonged close contact. Skin lesions themselves also are contagious. Travel history is the key, be sure to ask about that for anyone with a nonspecific febrile illness. Incubation period is about 5-13 days, easily long enough to allow for international travel before symptoms begin.

Myocarditis Concerns, and Delta Marches On 2

Bud WiedermannJune 27, 20212 Comments

Better Data on Risks of Myocarditis and Pericarditis from COVID-19 Vaccines

The ACIP/CDC held their meeting, postponed from June 18 due to the new federal Juneteenth holiday, on June 24. It was worth the wait, and fortunately I was able to attend the meeting online. You can see all of the presentation slides on their website, in particular I'd recommend the risk-benefit discussion by Drs. Wallace and Oliver. I had 2 major take-aways from the approximately 5-hour presentation.

First, as more time and cases have accumulated, the link between vaccines and myocarditis/pericarditis in adolescents and young adults (primarily male) seems much more convincing. The timing after the second dose, the striking age distribution, and the mostly mild clinical features strongly suggest a link even though the rates are very rare. It is worth mentioning this potential risk to people considering vaccination, though in these same demographic groups the risk of adverse sequelae from COVID-19 disease itself is much higher. Also note that this association was seen with both of the mRNA vaccines, Pfizer and Moderna, but I don't think we have enough information yet to know if this will occur with other COVID-19 vaccines. The mechanism of injury is still unknown and is the subject of much research.

Second, recognize that the only reason this was brought to light so quickly is that we have very massive and effective surveillance of adverse events with these vaccines. Please encourage all of your patients to sign up for V-safe when they are vaccinated, and everyone should report any suspected vaccine adverse events to the VAERS system.

Delta Variant is a Real Problem Everywhere

Evidence continues to mount that the SARS-CoV-2 delta variant is a major problem worldwide. It is unquestionably more easily transmissible than other variants by a long shot. Both mRNA vaccines seem to provide very good protection against severe disease caused by the delta variant, though preliminary data suggests that a single dose, rather than the recommended 2 doses, is not very protective. The jury is still out about whether delta causes more severe disease than other variants, but clearly this is the strain responsible for the vast majority of hospitalizations in developed countries, primarily impacting children and young adults who represent a disproportionate number of unvaccinated individuals. It likely will be the dominant strain in the US in a matter of weeks. Please encourage everyone to be vaccinated.

Somewhat more in the rumor category, a "delta-plus" variant has cropped up in the lay press. It is a strain that carries an additional mutation, K417N, that was known to be present in the beta variant and has been associated with poor response to treatment with monoclonal antibody preparations. We still need more information about this new sub-lineage strain to know its clinical significance.

Ebola Redux

Bud WiedermannFebruary 20, 2021Leave a comment

COVID-19 is still going strong, far outstripping my lame intentions to post something weekly. I have been keeping close tabs on all developments, but I feel like I would need to post a few times a week to be useful and I can't seem to make time for that. I do hope to give a COVID-19 summary update at the next Montgomery County Pediatric Society virtual meeting on March 8. In the meantime if you have particular questions please use the Comments section to pose them.

This week the news media finally seemed to start paying attention to disturbing developments in Ebola virus infections in both East and West Africa. It's worth discussion, especially since the world is much better prepared to handle it now than it was during the large outbreak in West Africa a few years ago.

First to East Africa, where we have new cases appearing in the Democratic Republic of Congo. The total number of cases is low, perhaps 6 (it's difficult to be certain of the exact number mostly based on media reports), but what is noteworthy is that the index case may have been infected by semen from an Ebola survivor originally infected in the 2018-20 outbreak in the DRC. Fortunately public health resources are being mobilized rapidly in a locale which like many other countries previously has had significant barriers to public health measures for Ebola control.

In West Africa, Guinea is the epicenter of a new outbreak. This was one of the countries, along with Liberia and Sierra Leone, most affected by the 2014-16 outbreak that spilled over into the US and elsewhere. Here the index case appears to be a nurse who first sought medical attention on January 18, was misdiagnosed for a time, and ultimately died on January 28. She was buried without safety protocols, further exposing others to the virus. As in the DRC, public health interventions are proceeding much more rapidly than in the past. As I write this, the World Health Organization is deploying staff to the area, along with millions of dollars in funding. Importantly, we have 2 main tools today that were not available in past outbreaks.

First, we now have specific treatment for Ebola virus disease in the form of a monoclonal antibody cocktail approved by the FDA a few months ago; results of a large trial were published in the NEJM in December. The trade name is Inmazeb, a bit less of a mouthful than the trio of monoclonal antibodies that make up the pharmaceutical: atoltivimab, maftivimab, and odesivimab-ebgn. It is effective in lessening mortality in infected individuals especially if given early in the disease course. Unfortunately it is administered IV so it is a little more cumbersome especially in resource-poor areas.

Second are Ebola vaccines. The US FDA approved one, called Ervebo, last December. It is a live recombinant vaccine made using a backbone of vesicular stomatitis virus (VSV) with the envelope glycoprotein of the Zaire ebolavirus substituted into the nucleic acid code. (VSV is primarily a disease of cattle, horses, and swine, and outbreaks have occurred in the US. Humans occasionally can be infected, primarily from direct contact with infected animals.) This vaccine is used to immunize contacts of Ebola virus patients in what is termed "ring vaccination;" the technique was highly successful in controlling and eventually eliminating smallpox, for example.

A second vaccine, not reviewed by the FDA, is available for use in other countries. It is actually a combination of 2 vaccines, a first dose Zabdeno which is an adenovirus-vector vaccine and a second dose called Mvabea which contains Vaccinia Ankara Bavarian Nordic virus supplemented with parts of various Ebola and related filoviruses. Because of the requirement for 2 doses, Zabdeno is not that helpful for immediate outbreak control such as with ring vaccination, but it is another tool to help contain the virus in a population.

The WHO announced creation of Ebola vaccine stockpiles just on January 12, 2021, good timing for what we are experiencing now. Immunization programs started in the DRC on February 15; vaccine shipments will arrive in Guinea on February 21 with vaccine campaigns starting on February 22.

Perhaps the US currently is at less risk for imported Ebola because of somewhat limited international travel, but we should not relax. Just as with SARS-CoV-2, any health crisis anywhere in the world affects all of us. Outbreaks in resource-poor populations can be devastating. I'm hopeful all the new advances in Ebola virus disease will prevent a repeat of the tragic 2014-16 West African outbreak.

Tag: vaccine