There's hopeful news about the possibility of an effective HIV/AIDS vaccine and a weird story from Canada about "preliminary results" saying that you are more at risk from swine flu if you get the seasonal flu vaccine. With flu, anything is possible, but that is more than a little counterintuitive and strikes me as unlikely. Nowhere else has reported a similar experience. Since we don't know the methods or the data or the limitations or much of anything else that could allow us to consider how much to weigh this as evidence I won't say any more about it.
While we do write about vaccines here because it's a topic in the flu world, vaccines are not one of our obsessions. We'd much rather see the hopes and efforts of managing the consequences of an influenza pandemic invested in public health's infrastructure, not redundant efforts to make a buck on a single target vaccine by multiple companies. Influenza vaccine is a public good and should not be in the market system. But that's another topic. Since all kinds of vaccines are the topic du jour, we will, for a change, muse a bit about vaccines ourselves. Because some of what we say might be interpreted as mixed or ambivalent and seized upon by a growing movement of poorly informed or misinformed anti-vaccination zealots, we should be clear at the outset about our convictions: we believe strongly that all children should be vaccinated against childhood diseases with the currently available recommended vaccines and that most adults should also be vaccinated with the currently available recommended vaccines. We believe this because it's the most rational choice given the evidence we have. I also believe it should be essentially mandatory for children and almost never mandatory for competent adults. We'll discuss the one exception we currently see, shortly.
While influenza vaccination prompted this post, we really want to talk about vaccines more generally because they present some interesting questions. To avoid getting into some hotly debated (although not, usually rationally debated) issues, we are going to make two assumptions which we consider have sufficient scientific support. First, that the currently recommended vaccines are acceptably safe (virtually no pharmaceutical is guaranteed perfectly safe), and whatever risks might exist are unequivocally overwhelmed by the benefits. And second, the implicit corollary of the first that the vaccines work. If you can't show a vaccine works or it barely works, then you shouldn't get it. We believe the currently recommended vaccines work, but if you don't, then you needn't read further. Still, even accepting these premises, it doesn't mean there's no more to say about safety and efficacy.
Let's talk first about testing the safety of a vaccine for a rare adverse event. You can't. If you have an event that strikes one in a hundred thousand, no clinical trial imaginable will be able to find it. If it's so rare, why care? Because when you are vaccinating hundreds of millions of people, rare events pile up. So you are reduced to counting up that pile, which as far as we know, is not negligible but miniscule compared to the pile of people whose lives were saved or whose disabilities were prevented by the vaccine. If the swine flu virus of 1976 had gotten out of Fort Dix and caused a pandemic like H1N1 already has, we wouldn't ever have worried about Guillain Barre or other rare events. But you can't know the extent of a rare adverse event, if one exists, until after you use the vaccine in the population. It becomes a problem in post-deployment surveillance.
The rare event problem is true of any pharmaceutical, or for that matter, any mass consumer product. Vaccines, however, are different on two counts. One is the huge number of people they are designed for. Still, there are lots of drugs, especially over the counter drugs, taken by as many people. Yet vaccines are almost unique in that they are being given to people who are healthy. They are not making sick people well. And the rare unlucky person who wins the (bad) adverse reaction lottery is plausibly someone might not have gotten sick in the first place. So it's not like the adverse reaction to an antibiotic or a cancer drug. And some vaccines -- and flu is an example -- don't have 100% efficacy and are designed to prevent a disease that for many people (mistakenly) don't consider serious and they further believe, for whatever reasons, they'll never get it. These are psychological problems, not rational risk benefit decisions. It's hard to think of any vaccine whose risk benefit balance isn't strongly in favor of the benefit. But it's clear that it affects how people think.
And maybe that's OK. I don't believe in mandatory vaccination for competent adults because I believe in the principle of personal autonomy. Children, who are not considered legally competent to make their own decisions, should have required vaccinations for the many diseases that killed and maimed them in the days before vaccination. I was a teen before there was a polio vaccine. I remember the horror of those days. Measles has almost disappeared and with it many infant deaths from that cause. The same for diphtheria, pertussis and mumps. And forget tetanus. There is nothing unusual about requiring vaccination for children. They are not permitted to do many things and are mandatorily required to do others (e.g., they have to go to school, they can't vote). There are provisions made for specified exceptions, as there should always be. But if an adult doesn't wish to be protected, I may think it's foolish but it's their choice. The one currently topical exception I lean toward is mandatory influenza vaccination for health care workers. My reasoning is that an infected health care worker comes in contact with people who are at greatly increased risk whom they may endanger by their choice not to get vaccinated. If they won't be vaccinated, they shouldn't be allowed to come to work in a health care setting. I work in a health care institution. I know this is controversial with health care workers and their unions. I am strongly pro union and pro worker. But I consider this a special case.
We are not particularly happy that the media coverage and discussion in the public square has focussed so strongly on the availability of a vaccine. It is, as we once remarked, planning for the best (an effective vaccine available in time to everyone) while hoping the worst doesn't happen. That's backwards from the way disaster planning is supposed to work (plan for the worst, hope for the best). But that's the way it's coming down, so we decided not to ignore it. It's a difficult issue that's not completely black and white. We'll keep our eye on the science and do our best to act rationally.
Difficult or not, a decision has to be made one way or another. We've already gotten the pneumovax vaccine for pneumococcal pneumonia and the current seasonal flu vaccine (not mention the shingles vaccine). When our turn comes for the swine flu vaccine we'll get that, too. We'll do it for ourselves, for our family, friends and co-workers, and for our community. A public health hat trick. You can't beat that.
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I got a little weepy over the HIV vaccine story last night, just because it's been such a long road here. Even though the efficacy isn't good, it's such a hopeful thing, after such a long struggle.
Believe it or not, given my--shall we say?--vociferous reaction to the anti-vaccine movement, yours is very similar to my point of view, particularly the dichotomy between what we require for children and what we require for adults. I'm less ambivalent about requiring health care workers to be vaccinated against the seasonal flu and H1N1, but perhaps that's because I work in a cancer institute, where there are lots of immunosuppressed cancer patients around.
Someone forwarded me a comment from an ER physicians who was strongly opposed to mandatory flu vaccination for health care workers. I was quite disturbed. After all, here's a guy who works in an ER, where lots of people will show up with flu or flu-like symptoms. He's a perfect potential vector. Ugh.
Orac, as a doc who works with hospitalized kids, I have so say the HCW vaccine issue is tricky. i always get it and so do >90% working on my unit, but overall as you know it's closer to 50% nationally for HCW, and it ain't 90% amongst my own docs though it will be higher than usual this year.
Just look at NYS for an interesting way to institute mandatory vaccine (regulation, no discussion). CT, where I live and work, will do no such thing. Sometimes how it's done matters more than what's done, though the idea that it's only 50%, mostly from misinformation ("I got the flu from the shot", which is impossible) is disgraceful.
@ginger So did I! So much so that I stayed up late writing a post on my blog about it ("The beginning of the end for HIV/AIDS? The RV144 HIV Vaccine trial in Thailand reports success" if you're interested)
It's been such a long time coming, although this particular trial was a little bit silly
Dem/Revere-You guys seen the stuff about seasonal flu vax making it easier for you to get Swiney?
Fascinating stuff-Side channels from Canada say that 5 people got H1 from the new LAIV and some honking big cases of it too.... Still waiting for something from Kings College to confirm that one. I hear a big oh-shit if it is true.
Interesting to say the least and the consipiracy nutz will have a field day with it of course regardless.
I generally agree with you, but as the mother of daughters, I'm not convinced about the risk-benefit ratio for Gardasil. I would hope (because it would be rash to assume) that my girls will be at little to no risk of dying of cervical cancer, even if they do get HPV, if only because I'll harangue them to get their Pap smears long past the age when I have anything to do with their health care. So I'm not sure I would tolerate any risk of adverse vaccine events, of which more than a few have been reported. I have a couple of years to mull it over, though.
I take a flu shot every year (not yet this year cos it was not available when I looked) as do the rest of my family. My kids have followed all immunizations as recommended.
I'm stating this right up front because I have discovered there's a tendency whenever vaccine debates come up, to pigeonhole someone as either anti- or pro-vaccine. It is a totally unhelpful attitude which just turns the debate into the kind of highly emotive and irrational mud-slinging that poses as 'debate' whenever the subject of abortion come up...
I'm neither pro- nor anti-vaccine - the subject is complex and important, and IMO deserves much more sophisticated discussion than such blanket labelling.
Not all vaccines are the same. They are tremendously heterogeneous, as are the people who will receive them. Vaccines look similar only to the extent that they all (or mostly) come in a syringe and that they stimulate the immune system etc. Beyond that, different vaccines vary widely in effectiveness and safety. The nature and the risks of 'vaccine-preventable' diseases also vary over a wide range, both in absolute numbers and in relative risk in specific groups.
Let's look at hepatitis B vs pertussis, both required in the current US mandatory immunization schedule. While some would consider the pertussis component of the DTaP vaccine as probably the most 'problematic', I still think there's a need to protect infants from whooping cough, which although rare is a dreadful and sometimes rapidly fatal disease that hit little babies. This vaccine therefore is targeted at the right age group, and it is also important to achieve sufficient herd immunity to protect every infant, including those who for whatever reason may not take the vaccine.
Now let's look at hepatitis B. In infants, the biggest risk of transmission is only present in those born to mothers who are Hep B carriers, which occur at only 1% for the US. Hepatitis B is also not easily transmissible during casual contact, the kind of contacts that kids might make in preschool or school. So the risk to 99% of young children is extremely low, and it is reasonably feasible to just vaccinate those infants born to HBsAg+ve mothers, as many countries do.
I've heard people object to this because of issues of stigmatizing. Others say it's harder to 'catch' kids for vaccination beyond infancy. The first is a social and perception issue, the second has to do bureaucracy and convenience (to the docs, not the patient). From the parent's POV, neither of these are good enough to submit their babies at a young age to 3 doses of yet another 'required' vaccine.
Which is why I have real problems with the mandatory issue. I think vaccines are powerful tools that protect kids, save a lot of lives, and that most kids should receive most of the recommended ones. I also think that whether a particular child should receive a particular vaccine should be a decision between parents and their doctors. The argument that removing the compulsion would result in dangerously low vaccination rates has very little leg to stand on because a) any such concern is only a reflection of the failure in public communication and especially in recent years, the loss of public trust, which should be addressed using transparency and accountability, not compulsion, and b) most other developed countries do FINE without such compulsions.
The biggest objection I have, is the combination of mandatory vaccination AND liability protection. I believe where liability protection exists, then the vaccine should not be mandatory. Remember vaccines are commercial products (until the day you, revere, can help change that!) the development of which are driven by profit. I know of NO other commercial product that is BOTH required AND protected from litigation. This is a get-out-of-jail free card for industry, a recipe for cavalier attitudes and sloppy science, and is IMO, at the deepest level, a violation of natural justice.
renee: I would have my daughter vaccinated if she were the proper age (she has kids of her own, now), but I don't think we have enough experience with this vaccine to make it mandatory and even if we did, I am ambivalent. So I basically agree with you.
SusanC: I know your position and frankly don't think we are very far apart, although I think we are a little ways apart. Regarding labeling a person as pro or anti, I again agree with you, which is why I wanted to state my own vaccine position as clearly as I could. It related to the current schedule of recommended vaccines. However in the US (an also for you folks in the UK) the power and distortion that is being created by an organized anti-vaxer movement cannot be ignored. It is having an effect on public health that is costing the lives of some children and denying benefits to many others. So we are walking a line and everyone walks it in a different way. Today's post merely represents my position and my way of walking it. There are other equally defensible ways (as well as many that are not at all defensible).
I absolutely agree, which is part of my motivation for writing about this. There's too much mis-information, leaving a lot of people confused and frightened.
I'm not sure the current HIV/AIDS vaccine will help. This is not a moral argument. I could care less if other people have sex or not before marriage.
Most of the general public think a vaccine is 100% effective. In fact, I thought so for most of my life. Given the 30% effectiveness of the HIV vaccine, I'd afraid that people will get it and think they are now safe from HIV and have more unprotected sex leading to an increase in cases.
The general release of that vaccine will need to have a side-by-side huge educational blitz. If not, I think the vaccine will actually make the situation worse not better because it will encourage risky behavior.
Hopefully, this is the road to a more effective vaccine down the road though.
George T: At least we now know a vaccine is possible. And 30% efficacy (one third less infection) is nothing to sneeze at. But now at least there is a path forward that's visible.
Today, the National Public Health Institute of Health of Quebec has reverse its vaccination program.
The seasonal vaccines is postponed to January at least because we expect that H1N1 will be way predominant this fall.
And one of the important point stated,
Doctor de Wals added;
Recent studies in Canada would indicate that people who have received seasonial vaccines in the last few years possible have higher risk of having an influenza of the pandemic H1N1.
Snowy
I think that the intelligent discussion taking place here is quite useful. I think that part of the power of influence that the extreme anti-vaxers have had comes from making vaccination into an all or nothing decision.
I believe that winning the confidence of average people will depend on building trust with the health care system and the governmental offices which regulate it.
I once to battle our major health provider to get a tetanus vaccine for a child about to go to summer camp. Apparently there was a shortage of vaccine at the time and they had decided to delay the boosters. And then wanted to stick to a rule is a rule is a rule. On the other hand, I have also battled doctors in order to separate vaccines (in order to isolate possible allergic reactions), or delay newly introduced vaccines (until more was known about issues identified as possible side effects). I terminated a relationship with a pediatrician who favored handing out free samples of Tylenol with vaccinations, which he actually explained as helping the babies fall asleep so that the parents did not get worried and call him.
Being able to do the above, depended of course on having the sort of flexible insurance plan that makes choice possible. I've seen headlines stating that some doctors are not doing routine immunizations because they are not adequately reimbursed for them. I wonder if there aren't parents out there who fall into an anti vaccine stance as a rationalization because in fact, they are financially unable to afford regular pediatrician check-ups. Public agencies are in a financial squeeze as well and do not have the right in the local elementary school immunization programs that were a feature of my childhood.
In order for the public to have confidence about vaccines or other medical issues, the medical establishment needs to demonstrate that it is acting based on intelligent thought and not out of economic self interest or expedience. And health care needs to be both affordable and accessible.
I think that the place to focus now in terms of promoting vaccines is health care workers. This seems to me to be a fairly clear cut case where generally it is in their own self interest as well as in the interest of the people they serve to get a flu vaccination. If they won't get a vaccine themselves, they are not very likely to be effective advocates for vaccinations, including the standard childhood vaccines for the public at large.
One comment. One question.
First, the comment. I saw the article yesterday about the "Canadian paradox" study which indicated that those vaccinated for seasonal flu were more susceptible to H1N1. Thanks to this blog, I read the article with an extremely critical eye and felt very little in the way of anxiety about it. So thank you!
Second, the question. My husband, who is 30, has a propensity for pneumonia. His body reacts to a simple cold by filling his lungs up with phlegm. Almost any respiratory illness require him to have antibiotics to stave off pneumonia. After reading this blog, I suggested that he get a pneumovax shot. However yesterday, his pharmacist said that given his age, he should already have been vaccinated as a child. I was just wondering if your pneumovax suggestion was limited to older adults? Or if it applied to younger adults as well?
Doesn't this look like an indication that there could be unexpected results regarding prior immunization and subsequent exposure to a novel influenza virus? I think this is important to address since it's possible that not only more people are getting the pandemic swine flu, but they could be having more serious outcomes. If this is the case, then it needs to be addressed immediately.
Paradoxical response to a novel influenza virus vaccine strain: the effect of prior immunization
Peter A. Grossa, b, c, *, Steven J. Sperbera, b, c, Armen Donabediana, b, c, Sandy Drana, b, c, Gail Morchela, b, c, Patricia Cataruozoloa, b, c and Gary Munka, b, c
a Department of Internal Medicine, Hackensack University Medical Center, 30 Prospect Avenue, Hackensack, NJ 07601-1991, USA
b UMDNJ New Jersey Medical School, Newark, NJ, USA
c Biological Support, ParkeâDavis Sterile Products Operations, Rochester, MI, USA
Received 16 July 1998;
revised 28 November 1998;
accepted 2 December 1998.
Available online 22 April 1999.
Objective: to determine whether the immune response to a new influenza strain was inferior in persons previously vaccinated compared with persons not previously vaccinated.
Design: randomized, double-blind clinical trial.
Setting: university affiliated community teaching hospital.
Patients: 139 healthy adult men and women, mean age 38 years.
Intervention: subjects were vaccinated as part of another study. They received influenza vaccines containing influenza strains A/Texas/36/91 (H1N1), A/Nanchang/933/95 (H3N2) and B/Beijing/184/93. One group received a licensed influenza vaccine while the other group received a similar vaccine except the A/Nanchang strain had a diminished potency.
Measurements: serum hemagglutination inhibition (HAI) antibody titers were determined prior to vaccination and two weeks afterward. If patients had a low postvaccination titer, they were revaccinated and HAI titers were determined two weeks later.
Results: 68 adults received the licensed vaccine and 70 received the subpotent vaccine. The groups were similar with regards to baseline characteristics. Those previously vaccinated had significantly lower postvaccination HAI geometric mean titers (GMTs) for all three vaccine strains (A/Texas â 127 vs. 359, p<0.001, A/Nanchang â 31 vs. 93, p<0.001 and B/Beijing â 140 vs. 205, p<0.05). The percentage of subjects with a presumed protective HAI titer of â¥40 was significantly lower among the previously vaccinated groups only for the new influenza strain, A/Nanchang (55% vs. 80%, p<0.05). For the other two vaccine strains, the percentage with an HAI titer â¥40 was greater than 90% for both groups.
Conclusions: the decrease in serologic response to influenza vaccine among healthy, young adults who were previously vaccinated appears to be unique for this year's influenza vaccine. Further studies are required to determine the frequency and clinical significance of this phenomenon observed in younger healthy adults, and whether it is a general one. Based on its proven efficacy, influenza vaccine should continue to be given on an annual basis to high risk children and adults and to all those 65 years or older."
Looks like that year had some big shifts in human H3N2:
Vaccine. 2006 Nov 10;24(44-46):6683-90. Epub 2006 Jun 16.
Reassortment between human A(H3N2) viruses is an important evolutionary mechanism.
"Strains isolated during 1998-1999 were characterised by a surprisingly high heterogeneity and multiple reassortment events. Seventy percent of the examined 1998-1999 viruses had completely different genome compositions. To our knowledge, such an exceptional high proportion of different reassortant strains, encompassing all eight genome segments, have not been described before."
Study below in swine showing dramatically enhanced disease in pigs vaccinated with mistmatched swine flu strain. (This effect, called a 'train wreck' is seen in the field at times. Pigs are less genetically diverse that humans, so this effect would be more scattered and harder to detect in humans.)
http://www.ars.usda.gov/research/publications/publications.htm?seq_no_1…
more from CDC today on the canadian study from Tom Frieden:
I am a primary care physician that specializes in Occupational Medicine. We are giving hundreds of seasonal flu shots a day to workers in Springfield, MO. With the "Canadian Problem" it seems that a two or three week suspension of our flu shot immunization program would certainly be prudent until we sort this thing out.
Am I being too quick here? How long does it take to get an article out of peer review and available for public (Revere!) review?
Addtionally, there are now additions that should be added to the informed consent form, right? The individuals being vaccinated need to know about the controversy even though the results are still being reviewed. Seems the entire country to our north is alarmed enough to take drastic measures.
First rule of medicine: First do no harm.
Thanks,
Gil
ellie: Hihgly unlikely he was vaccinated as a child, but adults get one with 23 strains, children only 7. He doesn't know his immunization. This should not be a bar to immunication. Here's the link: http://www.immunize.org/askexperts/experts_ppv.asp
Emily: Yes, of course it's important to address. There are already trials involving multiple vaccines given simultaneously and serially. And the paper is being peer reviewed.
Gil: depends on the journal but this will certainly get expedited review if it's a high profile journal; however it could get rejected or sent for revision if there are serious concerns from reviewers, so it's hard to say. I expect we'll hear soon because it's creating problems and there are discordant results from elsewhere (see Dem's comment at #16). We just have to wait to see. The informed consent thing is unclear since this is still in the rumor stage.
renee and revere: Gardasil was invented for the purpose of protecting women (and men) in countries where routine cervical screening is not available for cost, access or cultural reasons (Vanuatu, Tibet, etc).
Given the situation with all pharmaceutical companies being for-profit, in order to get the vaccine into production, it had to be widely marketed and taken up in first-world countries as well.
So, whether or not you feel it is applicable in your individual situation, the genesis of the vaccine was to help protect people who don't have the opportunity to protect themselves through regular screening. Without support and sales in the first world, the vaccine probably would never have become available at low cost to those who need it most (as much as that irks me).
child of gardasil inventor: I know the Gardasil story and the far different situation of the developing world where women still die of cervical cancer at horrendous rates. I was only addressing the question of whether it should be mandatory for US children. I would voluntarily have my daughter vaccinated but its safety record in the target age groups is still very sparse.
I think that part of the problem with the Gardasil vaccine is that the required age for immunization is much younger than many children would be expected to be sexually active. And, the immunity may not last long enough to even get to that point.
In an idealized society this vaccine could be handed out as part of a prior to sexual activity gynecological exam and planning visit. The risk/benefit analysis would be different because you could wait on the immunizations and maybe save a whole cycle some of the time. But in that sort of society of course, Pap smears would also be readily available.
Many of us are considered "too late" for this vaccine in that we are assumed to be already exposed to the HPV virus. Some of us will have been fortunate enough to have built up an immunity on our own. As far as I know that is not something that can be tested for at this point in time. From a pure medical, non profit motive point of view, it might be better to have an immunity test coupled with rigorous Pap smears especially for those most at risk.
As I understand it, the vaccine is known to be effective for only 70% of the viruses that cause cervical cancer. Don't we need to know if the other 30% is more or less likely to create immunity rather than cancer than the 70% being immunized against? Over time, is there likely to even be any overall decline in exposure to cancer causing HPV's? Maybe we'd only be changing the HPV distribution and the vaccine is only a short term fix.
Gaythia: It's important to note that being vaccinated with Gardasil does not mean a woman doesn't need to get a Pap smear on the recommended schedule for those not vaccinated. You still should get a Pap smear. The manufacturer of the vaccine stipulates to this.
I do understand that Pap smears are still necessary. I thought that the overall issue, had to do with the relative societal costs and benefits of focusing on widening access to Pap smears rather than administering the vaccine.
Certainly, this may be a problem going forward, if women who have been vaccinated are lax about getting their Pap smears.
But I am still curious to know what is known about the 30% of potentially cervical cancer causing HPV viruses that are not covered by this vaccine.
Dear Mr. Revere,
Thank you for condescending to discuss the plebian topic of vaccine safety and efficacy.
I am the mother of four high functioning autistic children. My mother was one of 13 children, my father one of 10. I had 60 first cousins. Six of us cousins were born in one year, 1953. I was the last to be born and the first to speak in complete sentences. My husband came from a much smaller family but in my husbands' and my families' cases not a single individual had the mutism and social difficulties of our children.
I have an MS in Industrial Engineering and a BS in Statistics. My husband is a bench scientist engineer. The exact sciences require exact results, verifiable, reliable, replicatable.
The arguments used in this post are consistent with the arrogant posture of so many of those in the governmental-pharmacuetical-medical complex, lacking in scientific citations while supporting broadly based historical assertions of the safety and efficacy of vaccines. No long or short term studies documenting the adverse events associated with vaccines using vaccinated vs. never vaccinated individuals has been done by completely unbiased researchers independent of government or the pharmaceutical industry ties. The argument implied here is the common medical assertion that genes are the cause of autism and improved diagnosis is producing greater recognition of the problem. As has been pointed out, if improved diagnosis alone is producing a larger epidemic of autism in appearance alone then where are the severely affected older individuals?
My family is a living refutation of that argument. I have an epidemic of autism in my family. All of my post 1990 born children are on the autistic spectrum - autism absent in the older family members.
I challenge you and the pharmaceutical firms you are associated with to a debate - in public - regarding the etiology of autism in my family - for a price - if you have the scientific balls to take me on. Just think, you can bring all of your deep scientific backfield to any debate - I have no one. Former "Catholic" friends shun me. "Catholic" bioethicists I've consulted argue in favor of mandatory vaccination. Even my own mother despises me and believes that genes alone( my father's in her opinion) are responsible for my children's autism. Hou can you lose? If you won't accept this challenge your credibility will be forever tainted.
My father was a poker player. I don't play poker but from him I learned that sometimes the only safe bet is to bet everything you have. I would bet my life that vaccines caused my children's autism and that is exactly what I believe it will cost me - my life.
Reveres,
I have tried to share with you a evident international upsurge in many languages that scientists are more and more daily considered as a currupted gathering of Science-Industries and Governments.
Unless something is done quickly by a strong group of Scientist.
Science will become in our collective memory the worst nightmare of Humankind.
Snowy Owl
Snowy: I am happy to have you share your thoughts here. I have been dealing with this problem for more than 40 years. It is not new. Scientists were integral to Napoleon's efforts, WWI and WWII, etc., etc. Before drug companies there was munitions and petroleum. Most scientists are not engaged in this way but many are. Most of us, like most people who are not scientists, are trying to live our lives but also, when we can, trying to make the world a better place. My silence on your comments does not indicate I have no interest or concern about what you raise. But we all work on this in our own ways.
Thank you Revere for your answer.
Snowy
Revere wrote: "...a weird story from Canada about "preliminary results" saying that you are more at risk from swine flu if you get the seasonal flu vaccine. With flu, anything is possible, but that is more than a little counterintuitive and strikes me as unlikely. Nowhere else has reported a similar experience."
This was my first reaction. But after being challenged by one of those irritating anti-vaxers who knows how to do a PubMed search, I've found a whole new area of immunology I was unaware of, that is, "antibody dependent enhancement". There are a number of articles on this topic referenced in the 4 page discussion on the FluTracker's forum and I did my own searching for articles to get a better understanding of this phenomena.
http://www.flutrackers.com/forum/showthread.php?t=126373&page=4
I really didn't want to know this. I felt comfortable with the miracle of vaccines and this research tends to be very disheartening. In some cases when one has antibodies to specific influenza strains, the immune system can apparently be dampened when infected by slightly different genetic versions. The body produces the 'near miss' antibodies (my term) in greater quantity than the effective antibodies. This has been referred to in the literature as 'original antigenic sin' (not my term).
http://www.cidrap.umn.edu/cidrap/content/influenza/swineflu/news/aug180…
In other cases the 'near miss' antibody in the presence of some antigens results in more efficient cellular uptake of the pathogen. There are a number of animal studies demonstrating this can occur with both influenza virus and the dengue virus. The studies describe what is going on at the molecular level but which I won't attempt to paraphrase here.
http://www.pubmedcentral.nih.gov/picrender.fcgi?artid=236853&blobtype=p…
Title: Subtype Cross-Reactive, Infection-Enhancing Antibody Responses to Influenza A Viruses
It's worth a quick review by anyone planning on discussing this potential new anti-vaxer material. We have not seen the last of the Canadian unpublished data with the unreviewed, unconfirmed conclusions about last year's seasonal flu vaccine impacting this years 2009H1N1 susceptibility.
And worse news may be on the horizon. As I was reviewing this topic I found at least one study that suggested antibodies to the 2009H1N1 vaccine strain may not protect people against the wild strain of 2009H1N1. In at least one study on pigs using an H1N1 vaccine strain against an H1N2 wild virus, the killed vaccine strain resulted in an enhanced infection with the wild strain.
That was the most disturbing result of all the research I reviewed. Because as I looked at the current state of the vaccine trials, it would appear they are in the stage of measuring antibody response. I don't yet see results that indicate these antibodies are indeed protecting people from exposures to the wild virus.
Here is a link to the study abstract:
http://www.ars.usda.gov/research/publications/publications.htm?seq_no_1…
Title: Failure of protection and enhanced pneumonia with a US H1N2 swine influenza virus in pigs vaccinated with an inactivated classical swine H1N1 vaccine
While I have no reason to change my firm conviction in the benefit of vaccines, this new field of study is concerning in the same way the medical community must have felt when the first cases of penicillin resistance began to appear. I'm confident the hurdles will be overcome. But I hope we don't lose people to infections we cannot prevent or treat in the meantime.
And with the 2009H1N1 virus already circulating, I hope we can see the evidence the new vaccine is effective against the new virus and not just effective at producing antibodies before I start giving it to my patients. I don't even want to think about the damage another swine flu vaccine debacle would do to our efforts to educate the public about scientific evidence based medicine vs news media superstition based medicine.
I'd be interested in hearing more about that Canadian study if it become available. My kids were vaccinated last year for flu for the first time. My son was never one to get sick with flu (He lived his first 2 years in a Chinese orphanage, so I figured he had built up a lot of immunity.) Mid winter and late winter, after the vaccine, he had 2 unknown (probably) viral infections with a reasonably high fever that didn't respond great to tylenol. He was out of school for about 4 days each time. It was curious to me that this was the first time that he had been noticablly sick with a flu like virus (he'd gotten ear infections and colds before).
Anyway I'm sure there alot of other explanations, we were visiting the hospital alot for therapy and tests, we changed schools, his china immunity stopped covering current virus, who knows. I was just curious.
Skeptigirl: There is indeed a literature on antibody dependent enhancement that I looked at a couple of years ago with respect to dengue hemorrhagic fever. So we know it happens, although I haven't seen it for flu, and many vaccines are polyvalent. For example, the adult pneumococcal vaccine has 23 strains in it. Because whatever we used to think about flu always seems to turn out to be different, I think everyone is waiting to look at the actual science done here, which most of us haven't had a chance to see. Since I am in the sausage making business I know all the things that can go wrong when you make them and as Dem's excerpt from the CDC presser (@16) shows, this effect is not immediately evident in other datasets. It's science and it takes time but it is happening as a real life pandemic unfolds, which makes it a balancing act for everyone concerned. You will see that even different provinces in Canada are adopting varying policies with respect to this finding.
@MicheleInMichigan
The new flu strain (2009H1N1) has spread readily through many populations that would not have had last year's vaccine. How much IF ANY increased risk of the new flu last years vaccine may have resulted in, it is unlikely it would have changed the risk benefit analysis for last year's flu vaccine.
In other words, even if I knew last year's vaccine would have an impact on the new flu strain, I still would have vaccinated the same population last year, including all children over 6 months of age.
One of the problems with getting medical information from the news media is the information is frequently turned into a fake crisis, a fake controversy, or a trumped up thing to fear. That's because the news is a commodity and crises, controversies and fear sell news. This news model produces colored glasses news reporters are trained to see the world through.
The attention this new flu strain has gotten in the media follows a predictable pattern. First, the fear mongering. While there was plenty of reason to take the newly circulating flu strain seriously, there is plenty of reason to take EVERY circulating strain of influenza seriously.
Then there was the predictable media attack on how public health handled the new strain. You need controversy to keep selling the news so now reporters turned to criticizing public health official's actions. In reality, the pandemic was handled very well, including closing schools at first, then not closing them when the data showed that measure to no longer be effective.
Making public health actions a fake controversy, of course, gave the public the impression the new flu strain was harmless and the health care community had cried wolf. But the health care community did no such thing. The news media, on the other hand, didn't care. Their job is to market the news. Their job is not to provide valid, actually useful information because that doesn't sell news.
So now the news media has a new fear and a new controversy to promote. It doesn't matter if the information is true, and more importantly, if the information is given in context. In fact, it sells news to take the information out of context by making it seem like seasonal flu vaccine is possibly dangerous, when the seasonal flu is just as deadly as the new flu strain so the vaccines for each are equally important.
If the media reported on the Canadian news leak information factually, first they would have waited for confirmation. Epidemiologists from the US and Europe are not seeing the same results.
Second they would have put the information in context. Knowing last year's vaccine would have increased the risk for the new flu strain wouldn't change the recommendation for last year's vaccine. That would have just put people at risk last year without having very much impact at all on the risk of the new strain. Your kids were going to be susceptible to the new strain regardless.
In the future you can expect the news media to continue hyping up the fear of the new vaccine. The media will make a point of selling the controversy that the health care community is going ahead with an untested vaccine. The media coverage will, of course, leave out the balance of the risk of the new influenza strain and instead rely heavily on reviewing the hindsight controversy of the 1976 flu vaccine campaign. 33 years of medical advances in influenza vaccine since 1976 will get little if any mention.
And when reports of medical events that occur after receiving flu vaccine occur, because people die and have medical events every day, vaccine or not, the mews media will play those up as if they are certainly a vaccine risk. Don't expect the news media to put those events in context. There might be a briefly mentioned caveat about ruling out other causes of the medical event. That will predictably be overshadowed by headlines declaring a dangerous vaccine side effect has emerged.
Then will come the scandalous public health actions of promoting an untested vaccine for a mild influenza strain.
Truth? Proper context? Doesn't sell news. It's not the news media's job.
Skeptigirl,
The problem with this is the fact that it was leak via one of the most respected Medical Journalist for years, Helen Branswell of the Canadian Press.
Plus the fact that tremendous heat was upon the Quebec Public Health when they decided to postponed seasonal flu shot and Dr De Serres who have publish the datas.
Snowy Owl
Respected or not, the reporting was typical news hype and not good scientific reporting.
Personally, I believe that it is unconscionable for HCWs to refuse to be vaccinated when they work w/ those most at risk and, as another commenter pointed out, ridiculously hypocritical to expect the public-at-large to embrace vaccinations when 50% of HCW refuse them; it really feeds the anti-vax paranoia: maybe the HCWs know something we don't know???
And, crap like this ...
http://www.naturalnews.com/027106_vaccination_Vitamin_D_vaccinations.ht…
After reading CIDRAP's
'Original antigenic sin': A threat to H1N1 vaccine effectiveness?
and
http://health.usnews.com/articles/health/healthday/2009/09/23/injectabl…
"Injectable Vaccines More Effective for Adult Flu Than Nasal Sprays"
As an adult, I will continue to get injections vs. the live-attenuated. I think I would prefer to get the H1N1 first, but not enough to risk waiting.
As a general rule, I hate the Examiner, b/c they litter our neighborhood with it, but I thought this was good:
Timing your (and your child's) flu and H1N1 vaccines
http://www.examiner.com/x-16797-Baltimore-Family-Examiner~y2009m9d23-Ti…
Having gone back and read multiple articles from Helen Branswell, I agree they are more thorough than most. They are accurate for the most part. It's a step in the right direction and I do not fault news reporters for doing their job which is to sell news.
But Branswell's articles follow the typical news media model and the result is predictable. For example, here is Branswell on the thimerosal issue: http://www.google.com/hostednews/canadianpress/article/ALeqM5gSlFg4Cq0N…
Title: Lack of thimerosal-free pandemic vaccine option leads some planning to pass
It follows the template of looking for controversy and scandal, despite its appearance of accuracy. There is a legitimate story here regarding the beliefs about thimerosal and the effect of those beliefs on a major effort to vaccinate the public, especially the at risk pregnant women.
But consider the amount of verbiage supporting the science. In the first 6 paragraphs describing the mercury fear you have, "experts believe it is safe. It's been used for years in vaccines," as the sole sentence supporting the science.
The next comment on the science is, "they believe some children suffer due to vaccination. Multiple high calibre studies have not supported the claim, but opposition to thimerosal persists in some quarters."
Which "quarters"? It suggests there is doubt about the safety of Thimerosal within the scientific community.
Next we have, "Dr. Michael Gardam, director of infectious diseases prevention and control at the Ontario Agency for Health Protection and Promotion, is convinced it is [safe].
"Personally, no, I'm not concerned about that," says Gardam. "(But) I'm not the pregnant woman getting the injection who's reading stuff about thimerosal and autism and God knows what else."
He admits he is worried that some people who should be in line for pandemic vaccine won't come forward because of the lack of a thimerosal-free option."
Gardam is worried. Those of us in the medical profession who are up on the vaccine research recognize the 'worry' in question is about false beliefs getting in the way of vaccinations. But the lay reader gets the overall impression from this article that the worry is bigger than that.
The report continues, "I have concerns that people won't get it because thimerosal is there," Gardam says. "People's concerns are their concerns," which puts Gardam on the side of the no-Thimerosal option. Again, I recognize the reason is to increase vaccine acceptance. But the impression is Gardam doesn't agree with the PHA of Canada's decision.
The following paragraph has the 'news media patterned' story of government scandal: "The Public Health Agency of Canada refused a request for an interview on the issue. Instead, a media relations adviser emailed material stressing that thimerosal actually adds to the safety of vaccine by preventing contamination that can result in bloodstream infections and abscesses.
"There is no safety reason to avoid thimerosal-containing vaccines," the email says."
The evil government conspirators are brushing off the risk.
The next two paragraphs are good. They make clear statements about the science. These paragraphs are 2/3 of the way down the page. They are countered by the bulk of the article. They are followed with more doubt about the science and more hinting the Canadian public health has made a politically convenient decision rather than a safe decision.
If I wrote this news story, it would be about the science and the problem with people who believe in non-scientific evidence based health claims. I would have written about how much harm the anti-vaxer Mommy web sites have been causing and the potential for deaths because of the false information those web sites promote. That false information, rampant on the Internet is the real scandal here.
BTW, this little paragraph in the Branswell authored news report on the Canadian data seems to be getting very little attention:
"The link, if real, is to mild disease. One person who has seen the study says it seems to suggest that those who got a seasonal flu shot were less likely to develop severe disease if they became infected than those who hadn't received the shot."
http://www.google.com/hostednews/canadianpress/article/ALeqM5g-jBo3N9xW…
Skeptigirl- That "antibody dependent enhancement" effect has been well known for decades. It's why there is no vaccine against dengue although it's easy to make - you can vaccinate against any of the three strains easily, but if they get one of the others it's far worse than it would have been without the vaccine. They are still working on a trivalent vaccine, which isn't so easy.
This same effect is seen in naturally occurring infections ... if you get dengue A and then get dengue B, you will be far sicker than if you only got "B".
So if (that's a big if) this effect is being seen with influenza, you are screwed whether you get the vaccine or not. If you get "seasonal" flu antibodies by vaccine or infection, then get "swine" flu infection ... it's still going to show the antibody dependent enhancement.
However, the persons most likely to get the seasonal shot in many places are also those most likely to have a serious case of swine flu: the ones with cardiac, immune, or respiratory disorders. Before you can claim an effect, you have to rule out the confounding effects such as the above-mentioned one.
***********
And to all you Gardasil IDIOTS, PAP smears are not "protective" against cervical cancer! They only enable early detection.
Skeptigirl,
Your post #31 is a great job of putting my perception of their philosophy and practice into words.
Bravo.
"If it bleeds, it leads, if it not bleeding, MAKE IT bleed."
Much appreciation to skeptigirl for the links re antibody-dependent enhancement. Now, people, another question: since a large proportion of persons who received last year's seasonal flu vaccine were over 65, and since the serology studies reported in the July 20 MMWR and Sept 10 NEJM (on which presumably are based CDC's recommendations that persons over 65 be last in line to receive 2009H1N1 flu shots)show in actuality a curve, with older seniors (especially those alive in 1918) showing very high likelihood of "immune"-level antibody response to 2009H1N1 and those born in the 1940s and even in the 1930s showing little more antibody response than middle-aged adults, are we not withholding vaccine from seniors who may have--if the Canadian study turns out correct--less immunity than many younger persons to the new flu? This seems particularly strange given that seniors have a 2 percent chance of death if they do get the disease.
Paula: You make a good point. The problem is that we know little about antibody dependent responses and they can be independent or work in the opposite direction. No one I know has actually seen the Skowronski data or methods. No one else is yet reporting such in effect in their datasets but we'll have to wait to see. We probably won't know much with any confidence for a long time after this event is over.
Regarding serology and its conflicting results. It is very hard to interpret this. The best evidence for me is not the serology but the epidemiology. If you are over 65 your are at dramatically less relative risk compared to your younger fellow humans than with seasonal virus. That includes people born in the 30s, 40s 50s, etc. So what the serology is showing us and what the epidemiology is showing us isn't quite consistent or clear. I got vaccinated for seasonal flu and will get the swine flu vaccine, too. Given all the evidence that's the most rational thing to do. If something changes, then we re-evaluate, but nothing has changed as far as I can see. There will be all sorts of conflicting pieces of data and at the moment we have to weigh them against the body of evidence we have. Don't be surprised if you hear next week or next month that having the seasonal flu is an advantage for swine flu and not a disadvantage. There's a lot of work going on and it is hard to evaluate it all simultaneously.
Thank you, Revere, for the thoughtful, considered response. I guess my concern with the epidemiology is that our actual data is so limited. And one Australian study (U. of Melbourne but I've lost the citation--in August, I think) reported finding no difference in apparent epidemiology between 2009H1N1 and any type-A flus, an interesting result which could mean, for one thing, that seniors are simply late in being exposed. Have you more info on this/related studies? I know Dr. Lipsitch of Harvard PH reported (or stated?) something similar recently to the IOM, though this may have been a general remark re the current statistics. Meanwhile, hearing seniors naively quoting reporters quoting the CDC that "Older people are at less risk, having been exposed to a similar, pre-1957 flu" gives me the creeps.
Paula: I think Marc was commenting on the CFR for swine flu and seasonal flu being similar, not the descriptive epidemiology, although I can't remember exactly the context either.
More data against a connection between last year's flu vaccine and the new strain.
http://www.google.com/hostednews/canadianpress/article/ALeqM5gXjwKAiS2b…
A preliminary analysis of data from hospitalized Canadian swine flu cases suggests there is no link between having a seasonal flu shot and developing a severe bout of pandemic flu, officials of the Public Health Agency of Canada said Wednesday.
They said the agency looked at data from hospitalized pandemic flu cases after learning of another, still unpublished study that seems to indicate people who got a flu shot last year had double the risk of catching swine flu compared to unvaccinated people.
Considering the over 65s would presumably have had higher rates of last year's vaccine and we know they have a lower rate of infection with the 2009H1N1, I'm wondering how researchers are factoring in or out that data.
As for the antigen uptake in the presence of antibody, the influenza animal study I linked to found the effect specifically in immune cells. Now I'm curious if the same cells are involved in the dengue infections.
Sigh... so much to learn, so little time.
Skepti: I did see this, and I am guessing previous vaccination with seasonal flu isn't a risk factor for swine flu (I say "guessing" because we don't know and don't have the data yet, but it's an educated guess, not a pure guess). However I noticed a little weasel word in this statement that made me wonder -- "severe". That made me think there is as yet an unresolved issue with flu infection. I think this could be best approached by releasing the methods and the data immediately. Put up a preprint so we can all see it. Delay in this situation is creating unnecessary confusion.
Revere, I guess I would like a bit of elucidation of your point (in 39), "the best evidence for me is not the serology but the epidemiology." I understand that, where these are in conflict, one needs to suspend judgment awhile, yet, as with awaiting the Perfectly Safe Vaccine, one has meanwhile to make practical decisions. Perhaps I should explain that, where I work, in rural Oregon, the local hospital's idea of "swine flu advice" is "Wash your hands!" and it is now offering free seasonal flu shots (not a word re the Canadian possibility) and telling residents to contact county public health (which suggests contacting the state) "or your physician, for swine flu shots," with many young parents eschewing all vaccines for their families and many persons over 65 out on isolated farms (and wanting the 2009H1N1 vaccine).
Paula: What I meant was the acid test is to see who is actually getting sick from this virus, not who has cross-reactivity in with a particular antigen in their sera. Even with serology there is conflicting data, with those over 60 having aout 1/3 cross reactivity, but decade by decade banked sera showing declining reactivity since 1918. Most of the former were not in their 90s. OTOH, very few people over 60 are dying from this compared to the usual age distribution for seasonal flu. Is that a bit clearer?
Revere, re 45--yes, I knew this; guess my question was unclear, sorry. I meant why choose as the acid test the epidemiological data, which may reflect exposure rather than percentage of immune persons, over the serology. Or perhaps I am asking if there is reason to believe this epidemiological data is not in fact tied to exposure levels.
Paula: Hmm. Well, it's hard to see why it would be tied to exposure levels since it is quite transmissible and exposure is quite general, but even so, that is an aspect of the epidemiology. As an epidemiologist I would never consider epi data to be the acid test, but in this case when the question is who is at risk of getting sick, it seems more pertinent to me than the confusing and conflicting serology data which is only indirectly and unclearly connected to who is getting sick. It'll take a long time to sort all of this out, so there's lots of room for disagreement and even more for confusion. And I admit I am confused by much of what I see.
Revere, I don't think I've expressed how much I respect this blog and the open, informed, honest discussion among contributors and editors here. A rarity to find so many persons who actually listen and respond to, rather than talk at, one another.
I'm wondering if others working in small rural counties have found at least the initial shipment(s) of 2009 H1N1 vaccine to be only a fraction of what would be their county's proportionate amount. Here, some lack of preparation has affected this, but does not seem to be the only factor. Anyone else seeing this problem? Should we assume this is "only" one of those "bumps" or soon to be straightened out?
Paula: Frieden's explanation of the roll-out here might explain what's happening.
Revere, thanks for the info in no. 50. Unfortunately the link "here" is not working.
Paula: My fault. Two errors in the HTML. I fixed it. Try again.
Thanks, Revere. Very kind of you. My other question on all this concerns what is CDC policy and what is from individual states, and what we may expect; specifically, Oregon provides 2009H1N1 vaccine reporting forms only for its 12 high-risk categories, which also leads to wonder whether the roll out will in fact cover all wishing the vaccine. In this county, the upset among over-65s with risk conditions is pretty strong.
Paula: I'm surprised that everyone who gets the vaccine isn't getting a reporting form. It's voluntary but I thought everyone was going to get one. As you will see in tomrrow morninging's post, the 65+ (me) are ttoward the bottom of th risk ladder for winding up in the ICU with flu-related problems. One of the few perks for getting old.
Revere, re 54, thank you. What I mean is that the state has provided reporting forms, with categories to check (for each of 12 risk categories), but none for the "everyone else" or the 65+'s. This makes me wonder whether there will be vaccine for these latter two groups here, in actuality, this flu season (assuming we can still speak in terms of flu "season"). Of course it is possible that someone the communications office is simply communicating poorly again.
Revere, I'm not sure where to place this post, but could you comment on the relevance, to the cross-reactivity/epidemiology contradictory data (re older persons and 2009h1n1), of the new Cardona/Zing paper (DOI: 10.3201/eid1511.090685
Suggested citation for this article: Xing Z, Cardona CJ. Preexisting immunity to pandemic (H1N1) 2009 [letter]. Emerg Infect Dis. 2009 Nov; [Epub ahead of print]
Preexisting Immunity to Pandemic (H1N1) 2009). Seems this could explain some of the contradiction (that is, allow for the possibility that the "33 percent of persons over [age N]" serology results might understate possible immune response) yet seems also that it no way indicates any one group as having extra immunity. Please elucidate, if you will.