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An Influenza Recap: The End of the Second Wave

We are nearing the end of the second wave of the 2009 H1N1 pandemic, and are now a few months out from the release of the vaccine directed against it.  Two topics have dominated the conversation: the safety of the 2009 H1N1 influenza vaccine, and the actual severity of the 2009 H1N1 infection.  Considering the amount of attention SBM has paid the pandemic and its surrounding issues, and in light of a couple of studies just released, it seems time for an update.

2009 H1N1 Vaccine Safety

This week the CDC released a report that evaluated the safety record of the 2009 H1N1 vaccine.  The first two months of the vaccine’s use were examined, from October 1st through November 24th using data from two of the larger surveillance systems monitoring the 2009 H1N1 vaccine’s safety: the Vaccine Adverse Event Reporting System (VAERS) and the Vaccine Safety Datalink (VSD).  This report represents the largest, and to date best, evaluation of the 2009 H1N1 vaccine’s safety profile since its initial testing and release.  The findings are reassuring.

We’ve talked about VAERS’ uses (and abuses) in the past.  Nevertheless, used properly as a surveillance tool, a “canary in a coal mine,” it can be quite helpful.  In that two-month span of time when 46.2 million doses of H1N1 vaccine were distributed, 3,783 adverse events associated with it were reported to VAERS.  204 of these events were classified as “serious,” including 13 deaths that occurred within 19 days of vaccine administration.

At first blush people may assume (unwisely) that the vaccine directly caused each of these reported events, and would thus yield an adverse event rate of 82 total adverse events and 4.4 serious adverse events per 1 million doses.  This is indeed the assumption (and mistake) made by people claiming for instance that the flu vaccine has caused X number of deaths or Y cases of Guillain Barre Syndrome (GBS).  Even taken (again, unwisely) at face value, these rates would be impressively low, particularly when compared to the risks of H1N1 infection, as we shall see later.

The story is even more reassuring once we look properly at the data.  It bears repeating that VAERS does not (nor was it meant to) establish causation, it only holds the potential to suggest a correlation.  We should also bear in mind that GBS, death, all adverse events in fact, occur at a baseline rate in the population in the absence of the vaccine (a hypothetical vaccine causing zero adverse events would still have a list of adverse events reported to VAERS reflecting the population’s baseline rates).  Thus to even determine if there is a significant correlation between the vaccine and any given adverse event, we need to determine not only how many adverse events occur in relation to the 2009 H1N1 vaccine, but the number that occur above the expected baseline.

That having been said, let’s examine the most concerning number first, the 13 reported deaths.  Each of the 13 are detailed on this chart.  It’s very much worth taking a look.  There is no discernable pattern to the ages of these unfortunate people, their underlying diseases, or their causes of death.  9 of these 13 people had significant underlying diseases, and one of them died in a car accident. Indeed, considering the population’s baseline mortality rate, it’s remarkable that only 13 people out of 46.2 million died within 3 weeks of receiving the vaccine by chance alone.  This doesn’t definitively exonerate the 2009 H1N1 vaccine from these deaths (well, we can probably safely rule out the car accident), but it certainly makes its involvement highly unlikely.

H1N1 Vaccine and GBS?

What of the concern of Guillain Barre Syndrome (GBS) following vaccine administration?  After all, at least one influenza vaccine in the last three decades has been shown to cause GBS in rare cases, and some poorly handled stories in the media have further elevated public concern.

The first two months of vaccine use saw 12 cases of suspected GBS reported to VAERS.  Investigation into these reports has confirmed four of these to be cases of GBS, four were not GBS, and the final four are still under scrutiny.

Again, these cases require context.  As the baseline rate of GBS is ~1/100,000 people per year, ~550 cases can be expected to occur in the US during the two months of this report.  These 8 likely cases of GBS in 46.2 million doses of vaccine is certainly not higher (and is in fact far less) than what one would expect to see by chance.  The VAERS database provides no reason to suspect the 2009 H1N1 vaccine has anything but chance correlation with cases of GBS.

H1N1 and Other Severe Adverse Events?

There is no correlation between the H1N1 vaccine and either GBS or death, but what of other concerning adverse events?  An evaluation of the 204 serious events reported reveals a scattershot of diseases, none of which have a signal that rises above baseline rates.

The CDC report contains a similar analysis using data from the VSD, where 438,376 doses of the H1N1 vaccine had been administered and adverse events tracked.  As with the VAERS data, no serious adverse events rose above their baseline rates.

In short, after the first two months of use and 46.2 million doses, the VAERS and VSD data fails to provide any evidence to correlate the 2009 H1N1 vaccine to any serious adverse event.  Given the seasonal influenza vaccine’s similar record over the past several decades, that the 2009 H1N1 vaccine continues to display an exemplary safety profile is not unexpected, but it is reassuring.

How Severe is 2009 H1N1?

What of H1N1’s severity?  What toll has it exacted?  The CDC has made detailed information, updated weekly, available to the public on its Fluview website.  Containing a wealth of information, there you can see 2009 H1N1’s unique and peculiar epidemiology, the unseasonable spikes in outpatient visits for influenza-like illnesses that have troubled our EDs for the last few months, and the trend of lab-confirmed influenza hospitalizations and mortality over time.

Hard numbers are also available.  As of November 28th, at least 31,320 people in the US have been hospitalized and 1,336 have died from 2009 H1N1 since August 30th.  The 2009 H1N1 has thus far claimed the lives of at least 250 children in between the traditional flu seasons, which is more than the two prior flu seasons combined.

This data is most helpful if viewed as the minimum confirmed impact of the disease, and as a catalogue of the most severe cases to date.  What you will not find on the Fluview site is the actual incidence of influenza infection, the total number of people infected, including minor infections.  This number is extremely valuable when trying to gauge the true severity of any infection, but fiendishly difficult to acquire.

A study published in PLoS Medicine this week contains one of the latest attempts to quantify 2009 H1N1’s severity to date.  Drawing from the data of two US cities during the initial wave of infections between April and July, they estimated that of all 2009 H1N1 infections, between 0.16-1.44% will require hospitalization, 0.028-0.239% will require ICU care, and 0.007-0.048% will die.

This study has garnered a significant amount of attention, for its estimates of severity are considerably lower (thankfully) than those made by the President’s Council of Advisors on Science and Technology in early August.  The accuracy and differences between these estimates, the inherent difficulty of determining the true incidence, severity, and future course of diseases like influenza warrants its own post, and I’ll not address this particular angle in greater depth here.

I’d like to instead reflect on what these two studies might tell us about the risks of contracting 2009 H1N1 compared to the risks of receiving the vaccine to protect against it.

On the one hand, we have a virus that has proven itself to be widespread and highly contagious, to have claimed the lives of at least 1,336 and hospitalized over 30,000.  Conservative estimates from the PLoS study place one’s risk of hospitalization if infected at ~1/625, and risk of death ~1/14,285.  Furthermore, though we have completed the second wave of the pandemic, a third wave is almost certain to come.  A small minority of the population has thus far been infected, past influenza pandemics have featured a triple peak, and we have now entered the beginning of the traditional influenza season.

On the other hand, we have an inexpensive vaccine which is an excellent match to this strain, generates an appropriate antibody response in most people (particularly those in the highest risk groups for 2009 H1N1), and after over 46 million doses has yet to be significantly correlated with any severe adverse events.

Conclusion

There are still a lot of uncertainties regarding the rest of this influenza season.  Will we have a third peak of H1N1, and if so, how severe will it be?  Will it continue to preferentially afflict the young, or will the elderly suffer a greater impact than they have to date?  How will the presence of 2009 H1N1 impact the normal flu season, will it be cumulative, or will 2009 H1N1 “crowd out” the seasonal strains?  The list goes on, and it absolutely includes the possibility that with ongoing surveillance and studies we may identify a serious but rare side effect caused by the vaccine.

As time goes on we will continue to refine our knowledge of influenza, and these questions will be answered, but it is unlikely that the big picture will significantly change.  Influenza is a virus with serious potential for harm that can be prevented by one of the safest interventions in modern medicine.  Please, particularly if you or yours are in a high-risk group, get vaccinated; I already know far too many of the names on this list.

Posted in: Science and Medicine, Science and the Media, Vaccines

Leave a Comment (22) ↓

22 thoughts on “An Influenza Recap: The End of the Second Wave

  1. Harriet Hall says:

    One could argue that the person who died in a car accident was the only one whose death was definitely caused by vaccination. He was on his way home from the clinic. If he had not gone to get the vaccine he would not have been in the car. :-)

  2. tcw says:

    Or that he had a syncopal event from the vaccine on the way home (which is why it is recommended that patients wait 15 minutes before leaving the clinic after a Gardasil shot).

    Any idea on the raw number of deaths given the mortality rate? If 100 million get H1N1, will 7000 to 48000 people die? Perhaps we could be looking at close to 100,000 deaths if 200 million people get it (I’m thinking only about the US)?

  3. windriven says:

    “Two topics have dominated the conversation: the safety of the 2009 H1N1 influenza vaccine, and the actual severity of the 2009 H1N1 infection. ”

    I would like to add a third topic: the inability to get the vaccine. I for one am still waiting. Doesn’t herd immunity require something on the order of 90% immunization?

  4. edgar says:

    Interesting MMWR article on mortality and sub-populations
    http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5848a1.htm

  5. Todd W. says:

    Dr. Albietz,

    Thank you for yet another great post on this topic. Good info to have available. It is wonderful that there is a source for this information, like SBM, since the media tends to ignore or misstate the issues.

  6. windriven says:

    Interesting article edgar. Do you have any information on cultural receptivity to vaccination in the AI/AN communities? Do you have any information on the availability of the vaccine in those communities? And wouldn’t this suggest that AI/AN populations should be considered ‘high risk’ populations in the event of future influenza outbreaks?

  7. edgar says:

    Generally most AI/AN communities are OK to all vaccines, although they have some of the same concerns (too many at once, etc) some Tribes do delayed schedule. I know of one Tribe that will not give polio, I have heard various reasons for this.

    I do not have info on the availability, but generally it is distributed through CDC to Tribes that offer vax in their clinics, and through the states through some that don’t (some Tribes are so small that their clinics and mostly referral only)

    However, there is something called GPRA, and it is a publically available data set, where you can look up vax coverage rates. Although interpret with caution, especially with vax, as low vax rates may be in indication of tracking issues and not coverage (i.e. a parent may go tot he health department for 1 or more vax, and that info does not get back into the system).
    As for being consider high risk, i think in practice they generally are, what with the high rate of diabetes and other chronic illness.

  8. SF Mom and Scientist says:

    windriven took the words out of my mouth. The biggest topic of discussion among our group was where the $%^$^% to get this vaccine. I was able to get my son both his shots before Thanksgiving and I felt like I won the lottery. The one thing I am hoping will come out of this is the development and acceptance of faster methods of vaccine testing/production. (I know this will give more “ammo” to anti-vaccine groups, but seeing as how they will never give up anyway, it is worth pursuing.)

  9. halincoh says:

    Nicely done as always. I finally get to receive my dose on Monday the 14th. People have wondered if they should still get the vaccine as the rates ( here in Maine ) decline. Protection against a possible “third wave” is a definite strategy as to answering them in the affirmative. Thanks.

  10. Deetee says:

    @winddriven – you ask “Doesn’t herd immunity require something on the order of 90% immunization?”

    That depends on the reproductive number (R0) of the infection you are dealing with. This indicates the number of people a case is likely to infect. For measles it is around 15, but for flu it seems to be between 1.5 and 2. An infection with a very low R0 will not spread widely, meaning that you need fewer people in the herd to be “immune” before it grinds to a complete halt.

    To estimate how many of the population need to be immune (vaccinated or recovered from infection) in order to negate the risk of epidemic spread, you can use the R0 in the following calculation:

    Proportion of population required to be immune = 1-1/R0.

    For measles this is 1-1/15, which is 0.933 (or 93%, which is why the aim is to achieve this amount of vaccine uptake to get herd immunity). For flu it is between 1-1/1.5 and 1-1/2, or between 33% and 50%.

    So it is possible that with only 1/3 to 1/2 of the herd being immune through vaccination or having had flu, that onward transmission would fizzle out. There are many other factors that could influence this however, and things are not always that simple (but it is still clear that you will not need 90% vaccine uptake to eliminate flu transmission)

  11. Calli Arcale says:

    I was in the emergency room with severe chest pain two days after receiving the 2009 H1N1 vaccine! EEK!!!

    I definitely will not be submitting a report to VAERS, though, as the cause of my chest pain was quickly determined to be esophageal spasm — my acid reflux disease (which I’ve battled for many years, and which runs strongly in my family) has apparently kicked itself up a notch. That, and I probably shouldn’t have had all that yummy, delicious rommegrot. :-P I’ll be getting an endoscopy next month, as it’s suspected that I’ve developed another stricture. Yay.

    Still, if I were an anti-vaxxer, I’m sure I would’ve believed there was some kind of a connection, despite the fact that I’ve had gradually increasing episodes of epigastric pain over the last month, leading up to this particularly severe episode.

  12. Zoe237 says:

    I have to agree with some previous posters. The story in this case isn’t so much with the media or the anti-vaxers. It’s about the fact that it IS the end of the second wave and millions are still waiting for the vaccine.

    I am curious though that it seem like a ton of HCP are not getting the vaccine. My husband did, but a lot of his collegues are refusing it, and advocating it only for children or immunocompromised people.

  13. Chrtowsky says:

    Does anybody know how many people were vaccinated to date in the US?

  14. wales says:

    Here’s one person who has not been vaccinated, and wins the irony of the year award. Buried toward the end of a December 29, 2009 BBC article titled “Swine flu virus ‘could still mutate’ WHO warns” is this somewhat mysterious line regarding WHO director Margaret Chan “However she admitted she had not yet had a vaccine but said she would have it soon”.

    Huh? I had to do a doubletake. December 29 and the WHO director still hasn’t been vaccinated for H1N1? What does she mean by “soon”? Doesn’t she heed her own warning about viral mutation? Surely the WHO director would have been given top priority, had she chosen to become vaccinated. Doesn’t she care about her responsibility to the world as WHO director, and her responsibility to prevent spread of H1N1 to her co-workers, family and friends? Is she some sort of vaccine “free-rider” relying on herd immunity?

    http://news.bbc.co.uk/2/hi/health/8434273.stm

  15. Chris says:

    My question is why is “libby” so intent on demonizing the influenza vaccine? She has been asking “Out of all the deaths from H1N1 in the US, how many were unvaccinated and how many vaccinated.” — and yet missed posting that question here.

    She did not seem to understand that there were more months between April 2009 (when the count of deaths started) to November 2009 (when the vaccine was available), than between November 2009 and January 2010. So she did not like my answer that the deaths before November were of people who were not vaccinated (and for those who are slow: it is because there was no vaccine), and then estimate the rest. At the present (late Jan. 2010) the CDC has reported that 20% of the USA population has been vaccinated:
    http://www.reuters.com/article/idUSN1521475420100115

    She also claimed some great stuff with Cuba and vaccine, claiming the literature was only available in Spanish. Unfortunately she did not count on Dr. Harriet Hall being fluent in Spanish. Apparently Cuba is not immune to flu:
    http://www.laht.com/article.asp?ArticleId=349456&CategoryId=14510

  16. Chris says:

    libby (from elsewhere, since it is off topic there):

    The solid hard evidence that confirms the effectiveness of the vaccine is this: of those who died from the H1N1 virus, We’re not evaluating trends, we’re not making a “good guess”, we’re not having to deal with the natural fluctuations of a disease as it moves through a population, nor the fact that a good percentage of people didn’t get the vaccine. It’s pure numbers.

    Furthermore this evidence is very easy to attain, since medical experts would have vaccinations records of all those how died. Easy info at our fingertips, except for one thing……I can’t find it.

    Since only 20% of the entire population has been vaccinated, and most of the deaths occurred before the vaccine was available, the answer is that it is too early.

    Look at the data here: http://www.cdc.gov/h1n1flu/estimates_2009_h1n1.htm

    Read this paragraph:

    CDC estimated that between about 7,070 and 13,930 2009 H1N1-related deaths occurred between April and November 14, 2009. The mid-level in this range was about 9,820 2009 H1N1-related deaths.

    Assume that no one who got the flu had been vaccinated, and remember this is a key concept: because there was no vaccine.

    Now read this paragraph:

    CDC estimates that between about 7,880 and 16,460 2009 H1N1-related deaths occurred between April and December 12, 2009. The mid-level in this range is about 11,160 2009 H1N1-related deaths.

    Now note that the vaccine had barely been available, but to only select groups. As of yet (I repeat) only 20% of the USA has been vaccinated. So it is a fair guess that the additional 1300 deaths (using the mid-level estimate) were not vaccinated.

    So the answer to why you cannot find the information you want (for some unknown reason) is because of insufficient data.

    Since the H1N1 vaccine is a monovalent, and it is designed for a specific virus (no guessing required like the regular bivalent flu vaccine) there are estimates that it is at least 90% effective (remember not everyone will respond to a vaccine, no matter how good it is, due to genetic variability). For more information on influenza, including a Virology 101 course checkout http://www.virology.ws/.

  17. libby says:

    Chris:

    You claimed I was demonizing the H1N1 vaccine by asking for evidence of its effectiveness. I never knew that asking for evidence could be seen as demonizing, especially on a site with “science” in its name.

    And to claim there isn’t enough data is remarkable. If 2 die from H1N1, you look at their vaccine records. If 10 die, you look at their vaccine records. If 100 die, you look at their vaccine records, etc, etc. We’re only talking about deaths from H1N1, nothing else.

    The more that die, the more accurate your ratio. This is just numbers.

    Chris states: “most of the deaths occurred before the vaccine was available” is totally irrelevant because you simply limit the scope of your analysis to AFTER the introduction of the vaccine, or any time period you want for that matter that will give you the best data.

    Someone else claimed there was a privacy issue on corpses (another astounding concept), but in any case, the numbers and ratios would not have to show names.

  18. libby says:

    I find Chris’s personal attacks quite risible if for nothing other than they are so clumsy.

  19. libby says:

    Oh and Chris, one other point.

    Thanks for quoting me and then EXcluding the correction of my post so that it actually made sense.

    (Of those who died from the H1N1 virus) HOW MANY WERE VACCINATED?

    That was my complete sentence, if the truth has any meaning to you.

    It’s amazing how such a simple question has created such a frenetic, nervous response.

  20. What is killing me (omgroflol) is that where I live, the Walgreens chain has had plenty of H1N1 vaccine throughout the season, yet neither my own doctor’s office in a major metropolitan medical clinic or my son’s pediatrician’s office had ANY, except for baby-sized doses. Sheesh!

    What’s the deal there? Does the CDC figure that more of it gets to the public if it’s available in drug stores rather than in various doctors’ offices? (They might be right– I’m just curious.)

  21. squirrelelite says:

    Libby,
    Thanks for coming to the influenza recap post to discuss influenza. While off topic comments can be useful or at least entertaining, it is usually best to stick to the topic at hand.
    I will mostly ignore the “demonizing” question because I don’t want to spend the time right now to chase down the original post where you asked about evidence of effectiveness. I will merely note that asking for data is not demonizing. However, implying or suggesting that; because the data available lack the detail, accuracy and completeness that you wish; the product under discussion is therefore somehow inadequate could be construed as such. I apologize if this is not quite what you were getting at.
    Keep in mind that the precision and accuracy of data always depend on time and money and the availability of other resources such as equipment and labor. Diagnosing that someone is sick with influenza or influenza like illness (ILI) is a relatively straight forward diagnosis, as is determining on a death certificate that they died from ILI or a related disease such as pneumonia. On the other hand, taking a genetic sample and determining the precise genotype of the virus so that we can accurately decide if it is the novel 2009 H1N1 strain or some other flu virus is a complex procedure that takes a lot of time and resources that simply are not available at the state health departments that conduct the tests. Probably it will be a lot quicker and easier in another ten years, but for right now, it’s not as easy as it looks in the CSI shows.
    So, that leaves us with the data that are available and which Chris noted in his comment. There are some inherent estimates, assumptions, and uncertainties which we keep checking against reality and adjusting for. Here is what I have teased out from the sources Chris mentioned and perhaps a few others.
    If you want carefully tested real data on whether the H1N1 vaccine does what it is supposed to (generate antibodies), here is an article about some published studies.
    http://www.medicalnewstoday.com/articles/174147.php
    The CDC estimates for 2009 flu that Chris linked to are good to keep up on.
    The weekly update reports are also good to check.
    http://www.cdc.gov/h1n1flu/update.htm
    Approval of the H1N1 vaccines was announced on 15 Sep 2009, with initial availability projected for 5 Oct 2009.
    Weekly percent of ILI cases peaked in most U.S. regions about weeks 41-42 (8 Oct-21 Oct 2009). Since then, there has been a sharp and mostly steady decline.
    The following table shows how we have gone from initial restricted availability in early October to the current situation where the vaccine is available to just about anyone who wants to get it.
    CDC Weekly Briefing Data
    Date Doses Available
    7 Jan 2010 136 million
    22 Dec 2009 111 million
    10 Dec 2009 85 million
    1 Dec 2009 70 million
    20 Nov 2009 54.1 million
    12 Nov 2009 41.6 million
    3 Nov 2009 31.8 million
    27 Oct 2009 22.4 million
    16 Oct 2009 11.4 million
    9 Oct 2009 6.8 million
    1 Oct 2009 600,000 doses ordered
    Here are the cumulative H1N1 Case Totals from April 2009 till the listed date, which Chris also referred to:
    Date Cases Hospitalizations Deaths
    17 Oct 2009 22 million 98,000 3900
    14 Nov 2009 47 million 213,000 9820
    12 Dec 2009 55 million 246,000 11,150
    So, from 17 Oct to 14 Nov there were 115,000 hospitalizations and 5920 deaths from the H1N1 virus. 0.0237% of cases resulted in deaths.
    From 14 Nov to 12 Dec, these numbers dropped to 33,000 hospitalizations and 1330 deaths. 0.0166% resulted in deaths.
    Since 18-19% of the U.S. population has now suffered through the H1N1 flu and another 20% has gotten vaccinated, almost 40% are now protected in one way or another. Some of the drop in cases from Nov to Dec was undoubtedly due to normal flu case load variation and the eventual decline in the disease as more people become resistant. Some of it probably resulted from availability of the vaccine and 20% getting immunized. The details just aren’t there yet to separate the two effects, but we can hope they will be forthcoming.
    Since there are four months left in the “normal” flu season, I have already gotten the seasonal flu shot and plan to get an H1N1 shot soon.

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