Tag: hepatitis B vaccine

I spent a miserable day and a half viewing the ACIP's deliberations on hepatitis B. The scope of the sessions, so far outside any resemblance to scientific discussions, made my conclusion remarkably straightforward.

Believe it or not, a few other notable notices and publications also appeared last week.

Single Dose HPV Vaccine Might Work

An article in the New England Journal of Medicine showed that single dose HPV vaccination is noninferior to 2 doses in preventing new HPV types 16 and 18 (the 2 genotypes that account for about 3/4 of cervical cancers worldwide) persistent infections in adolescent girls. The fact that this was a noninferiority trial should be noted carefully - the trial didn't have enough enrollees to assess whether the 1-dose region was truly equivalent versus slightly better or slightly worse.

They started with 20,330 healthy 12 - 16 year-old participants in Costa Rica randomized equally into 1 of 4 groups: 1 or 2 doses of bivalent HPV vaccine and 1 or 2 doses of nonavalent HPV vaccine. An unimmunized group of 3005 participants also were included. Subjects were followed for 5 years.

It's mandatory that noninferiority trials include a prespecified margin of difference between the groups to define whether a particular regimen is noninferior to another. In this study, the margin specified was 1.25 infections per 100 participants. When all was said and done, about 4000 participants in each of the vaccine groups and just under 3000 unimmunized participants were included in the analysis. The table below shows that the single dose vaccine regimens were well within the noninferiority margin as seen in the 2 rate difference columns.

Vaccine effectiveness of both vaccines, compared to the unimunnized group, against the 2 major genotypes was in the high ninety percent numbers, and even the lowest level of the 95% confidence intervals was still a robust 94.3%. Of course the bivalent vaccine, which contained only HPV 16 and 18 components, was much less effective for the other genotypes.

The ability to administer just 1 dose of HPV vaccine would have very important ramifications worldwide, especially with deep cuts to international preventive care funding. For the US, the current AAP immunization schedule recommends a 2 dose HPV vaccine regimen to be offered starting at 9 - 12 years of age. It will be interesting to see whether these recommendations might change.

Miscellaneous Outbreak News

The infant botulism outbreak associated with the ByHeart Whole Nutrition Infant Formula has now reached 39 cases, as of December 3. It is concerning that FDA is still reporting that the formula remains available for purchase in some stores even though all products from this company have been recalled. CDC has a nice page with concise advice and links.

Also on December 3 the CDC Health Alert Network posted an alert about the Marburg virus outbreak in Ethiopia; not sure why it took so long. It didn't contain any new information from what was reported from WHO and mentioned in a previous blog post.

Measles is still rolling along steadily in the US with case count 1838 on December 3. Utah, Arizona, and South Carolina are the main hotspots, and all recent cases were acquired in the US rather than from foreign travel.

Finally, some good news. The Ebola outbreak in the Democratic Republic of the Congo is officially over. The tally was 64 cases, 45 of which were fatal.

WRIS

The winter respiratory infection season is starting to kick in, though the national average still qualifies as low activity. Influenza-like illness, which includes other respiratory infections beyond influenza, is patchy.

I somehow missed that fact that last week was National Influenza Vaccination Week. Let's hope it did some good. Please encourage your patients and families to be vaccinated.

ACIP Reaches Irrelevancy

I suffered through a day and a half watching the ACIP deliberations on hepatitis B vaccines. It would be sort of a whack-a-mole endeavor to address every instance of misinformation or worse; one attempt at fact checking the meeting was posted by The Evidence Collective. It's a sorry sign of the times that we even need such a website.

Instead of going over every instance of misinformation or worse, I'll focus on some key general issues I observed.

• Lack of structured approach to evaluating evidence. ACIP Work Groups do a lot of the pre-meeting heavy lifting of data assessment, in the past relying heavily on subject matter experts from CDC and other institutions. As I stated last week and many times in the past, ACIP should follow a predetermined, standardized process for evidence evaluation and present those results at the meetings. This was standard in the "old days," relying on 2 processes: GRADE and Evidence to Recommendations (also mentioned last week). These systems not only analyze the data but present the level of confidence in the results. EtR provides in depth discussion of different components to consider when making a recommendation and includes vote tallies/opinions of working group members. It was clear this didn't happen for the hepatitis B discussions, leading to ....
• Cherry-picking of evidence. The Work Group leadership presented whatever she/they thought was relevant, seemingly to support a pre-determined outcome.
• Overt ignorance (presumably deliberate) of recently published key studies.
  • The very biased presentation on aluminum adjuvants (I didn't listen to it in entirety, it was clear very early it wouldn't be worthwhile) didn't mention in its 28-page slide deck a new review publication (with 469 references!) concluding "Collectively, the evidence strongly supports the safety of aluminum adjuvants and their necessity in certain vaccines. Clinicians can reassure caregivers that aluminum-containing vaccines provide clear benefits, with risks largely limited to transient local reactions and no systemic toxicity signal in large clinical and epidemiologic studies."
  • Similarly, no mention was made of the Vaccine Integrity Project's detailed report on hepatitis B vaccine safety, effectiveness, and public health impact.
  • A new viewpoint article on risks of altering the hepatitis B vaccine schedule in the US was enlightening but ignored by the ACIP. Using reasonable, conservative estimates for variables such as annual birth numbers, vaccine effectiveness, loss to follow-up, and others, the authors estimate that the new ACIP recommendations to not immunize newborns of HBsAg-negative mothers, if followed, would result in an increase of perinatally infected infants from 625 to 674 per year. Given that perinatal infection usually results in a chronic carrier state that leads to cirrhosis and/or hepatocellular carcinoma decades later, this is a very serious increase. Because of the long lag time in symptoms of chronic HBV infection, we likely won't know the consequences of the ACIP changes for decades. Also, this strategy increases the chance that these children would not be immunized as adolescents or adults, leaving a much larger susceptible population in the US. It would have been very helpful to include this information in the ACIP discussion.
• Moving targets. This is another whack-a-mole strategy. When one concern, like hepatitis B vaccine safety, is raised and seemingly rebutted, another concern such as parental choice (which has never been removed) is brought up. And on and on.
• Lack of knowledge. This was most obviously on display by all of the ACIP members including those in favor of the current hepatitis B schedule. It's not surprising that ACIP members wouldn't know everything about the current state about hepatitis B infection and vaccines, even the one person who had any legitimate vaccine experience and knowledge. However, plenty of people do possess this expertise and were available to committee members. They were seldom consulted.
  • In a decision not explained by ACIP leadership, the ACIP's chosen presenter on the entire childhood vaccination schedule was an attorney specializing in vaccine injury. At least he mentioned conflicts of interest honestly, with his firm having several hundred pending lawsuits against the government for vaccine injury. This isn't the background for someone to give me a valid overview of vaccine schedules.
• Subtle barriers to subject matter experts. In the "old days" ACIP meetings were held in a large auditorium with regular members, ex officio members, liaisons from other organizations, and SMEs mostly all present in the room. Now, the meeting is in a smaller room populated only by members, ex officio members, and selected presenters. The ex officio members and SMEs, representing the majority of the scientific knowledge of the subject, were occasionally allowed to speak but their faces were never shown and they seemed (to me) to be more frequently interrupted by the ACIP vice chair who was running the meeting, in contrast to fewer interruptions of the anti-vax members of the group. This was a not-so-subtle dehumanization of the true experts. (One rational CDC expert, Dr. Langer, was shown speaking when he was called upon a few times; he is in a leadership position at CDC so apparently not sequestered with the other SMEs. He was excellent and obviously trying his best to politely push back on incorrect statements from committee members.)
• Late posting and frequent changes of meeting agenda, voting statements, and slides. Less time to review these documents ahead of time results in less time for non-ACIP members comment appropriately. This strategy effectively dampens ability of everyone involved to discuss their views.
• And coupled with the above, the discussion times allotted were very brief, especially given that GLOBE and EtR results weren't provided. This resulted in ineffective discussion at times dissolving into temper tantrums.

I could go on and on with this list, but I won't bore you any further.

The final recommendations centered on 2 votes. This first one was highlighed in the lay press is replete with mention that the hepatitis B vaccine recommendations from ACIP have changed with regard to infants born to mothers who tested negative for HBsAg sometime during pregnancy. Recommendations for infants born to mothers who are positive or who have unknown status haven't changed. There was little to no discussion on the long-term ramifications of this decision.

My final conclusions about the meeting were most affected by the approval of the second vote. It recommended (presumably just for the infants born to negative mothers, but it didn't specify) that parents could decide to obtain a hepatitis B antibody titer after a first vaccine dose to decide if subsequent doses would be necessary. This completely ignores the fact that no one has any data on how this single titer would relate to evidence of protection and doesn't even consider the role of maternally-derived antibody present in some infants. There was no discussion about the antibody test itself - why the various cutoff values were decided upon and how they have been studied. The entire statement in that second vote seemingly was pulled out of a hat.

For me, that was the last straw showing that the ACIP isn't serious about evidence-based guidance. The vote 2 approval wasn't fueled by cherry-picking data, because there was no data. This was acknowledged by the vote 2 proponents. The vice chair even voiced his glee at the fact that implementing vote 2 recommendations would be a great experiment to see what happens. The press apparently missed this statement; I think most parents would be horrified.

ACIP, in its present state, is irrelevant. We can disregard their recommendations and look to AAP and other reliable organizations for our vaccine schedules and recommendations. I've already received notice from the Maryland Department of Health supporting universal birth dosing of hepatitis B vaccine and for all infants to complete the full hepatitis B vaccine series.

Crying in My Chianti

Friday evening after taking a mental beating listening to the meeting, some friends joined my wife and me at an Italian restaurant in part to console me and provide a diversion. Table talk ranged from current movies to Royal Doulton Toby jugs. It worked very well, only a few tears in my wine glass. At least I won't feel the need to slavishly attend future ACIP meetings.

In the meantime, in addition to noting it's time to change my view of the ACIP, I'm also going to change this blog site. I will take a partial hiatus from the blog, posting less content and perhaps less frequently for a while. Instead, I'm going to try to spiff up some of the web site appearance and add some more pages beyond just the blog; I serve as both content creator and IT support for this site. I don't have an exact timeline for the revisions, but I will continue to post, especially for the most impactful happenings in pediatric infectious diseases.

If you have any suggestions for how I can improve the site, please let me know in the comments section.