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More Flu Woo For You, Boo Boo

In which we try to be smarter than the average bear.

Flu season is upon us (it kind of never left us this year), and there is a new strain of flu, the H1N1, aka Swine flu that adds a wrinkle or two to the usual potential for influenza related morbidity and mortality. And with the new flu is the new woo. I know that others have addressed flu in this forum and some of this may be redundant. Still, we each have our different styles and interests, so I hope the various posts are additive rather than redundant. I am going to wander through some odds and ends about flu in general and H1N1 specifically and compare some of the woo with the reality. At least my reality.

Influenza and Vitamin D

Influenza can be prevented or treated with Vitamin D. Don’t tell that to Dr. Marshall. The Natural News, the source for all things over hyped and under understood (Ick. That parallel form didn’t work.), is a nice example of the hype of Vitamin D as a preventative an treatment of influenza.

Vitamin D is an interesting molecule. Besides its long known effects on bone metabolism, Vitamin D has many immunomodulatory effects and is an important vitamin for immune function. Vitamin D even has effects on nitric oxide regulation. Its effects on infection risks are just beginning to be elucidated but deficiency states (note deficiency states) are associated with an increased risk of viral respiratory infections and worsening of pulmonary tuberculosis.

Again, deficiency states. If you are replete in your Vitamin D, there is apparently no immunologic advantage in taking extra, as seems to be the case with all vitamins. Metaphorically, if the tank is full of gas, you can’t go further by pumping more gas into the tank.

Vitamin D deficiency is not uncommon in the Northern Latitudes especially in the winter and in populations who have little sun exposure (nursing home patients). So like all deficiency states, it is reasonable to fill the tank, with extra Vitamin D. It will probably decrease the chance of getting a viral respiratory infection. In general, supporting data is limited and the effect small, as a review points out (2).

How about Vitamin D specifically for influenza?

There, the data is limited and mostly epidemiologic, but interesting none the less. The natural news, which states “In the realm of peer-reviewed medical literature, searching Google Scholar for “influenza” and “vitamin D” returns tens of thousands of results (http://scholar.google.com/scholar?q…).”

Interestingly, using influenza and dental floss for search terms on Google scholar results in over 1500 articles; it is hardly the source for the peer reviewed literature. If you use Pubmed, the source for peer reviewed literature, there are 30 references, not tens of thousands, and less than a half dozen specifically concerning vitamin D and influenza.

The reasoning goes like this: flu increases in the winter. In the winter people get less sunshine and their vitamin d levels drop. Therefore it is the vitamin d deficiency in the winter that predisposes to influenza. Of course, people crowd together inside in the winter, increasing ease of transmission and flu occurs in the tropics where it is always sunny, so it is probably not the only reason flu increases in the winter. But it may well be a small component,

It is biologically plausible that vitamin deficiency increases your risk for infection, there is reasonable epidemiologic data to support the association, and it is not unreasonable to be replete in you vitamins.

What is neither reasonable nor supported is to take supratherapeutic amounts of vitamin D as a replacement for either the vaccine or, if you should get flu, oseltamivir.

Vitamin D is not ” is perhaps the single most powerful nutrient in the known universe for preventing influenza, ” despite the Natural News hysterics. Yet another alternative mountain made from a scientific molehill.

SURVIVAL OF THE FITTEST

Use of the vaccine is counterproductive. Use of the vaccine will lead to a superbug.

I have found this on the webs and from a letter to SBM, and I can only speculate where this idea originates.

Antibiotics can breed resistant bacteria and resistant organisms are often referred to a superbugs. The resistant organisms may not necessarily be more virulent. Just because the bacteria may be harder to kill with antibiotics doesn’t necessarily mean it is more invasive. Sometimes, like current strain of methicillin resistant staphylococcus, may also has a high incidence of carrying genes that increase its virulence. However, as best I can tell, the increased virulence genes of the USA 300 strain are independent of its antibiotic resistance.

There was an interesting report in Clinical Infectious Diseases that suggests that as a result of anti retrovirals, perhaps HIV is becoming more virulent. It can happen as a result of antibiotics, but it is unpredictable.

Certainly if you markedly decrease a pathogen in the community, those who would have died in the past are more likely to survive and pass on their susceptibility to their offspring, increasing the vulnerability of the population to the severe disease. Put’ toll’, ‘infection’ and ‘polymorphism’ into Pubmed to find a growing literature on the genetic susceptibility for getting and dying from various infections. Historical epidemiology out of Utah suggests that the risk of death from influenza is inheritable.

So what you might expect is after long term vaccine use allows for the accumulation of susceptible hosts in a population and if there is a decline in vaccine use that there will be an increase in morbidity and mortality when the disease returns to a more susceptible population. So it may not be due to a superbug, but a susceptible population; increase in death due less to the organism and more to the host.

So can vaccine induced immunity lead to a superbug? It has not yet happened, but it does have some plausibility and it depends on the virus. Widespread use of smallpox vaccine did not lead to a super-small pox, it lead to the eradication of small pox. But, some viruses, due to sloppy reproduction, as occurs in influenza, can alter their surface proteins (where antibodies bind) to escape the immune system. So widespread use of the vaccine could (and should?) lead to new strains of influenza that avoid the antibody. But, and here is the key thing, that happens with normal infection.

As the flu season progresses the organism slowly changes its surface proteins (aka genetic shift) so that the strain at the end of the season is different than the strain at the beginning of the season, part of why we need a new vaccine every year. However, these mutations as a rule do not make the organism more virulent. That usually requires both a genetic shift (new genes) and bad luck (the organism getting the ‘right’ new genes) and this process is not affected by immunity. So it seems unlikely that widespread use of the vaccine would lead to a superbug. So you can potentially put immunologic pressure on influenza to change two ways: my getting the vaccine or by getting the flu. Both will lead to antibody against the organism, but only one will make you sick and potentially pass the infection on to others. But the end result will be the same.

A NEW WORLD ORDER

There is this weird paranoid thread running through the internet that the government simultaneously wants widespread use of the vaccine to line the pockets of doctors and big pharma, and to control health care costs by releasing a laboratory derived influenza culling the ill who cost society the most, and to cause widespread panic so that the UN can take over the US and install a new world order.

H1N1 is not going to be a very good way to either decrease costs or to cull the most susceptible.

First, H1N1 is highly infectious but not particularly virulent. While the 1919 H1N1 killed maybe 5% of the population, the current H1N1 has a mortality rate of 0.6%. Since this is based on hospitalized cases, the true death rate is probably much less. The groups most at risk of dying from H1N1 are those less than 60 and healthy. So if you were trying control costs by killing the most at risk, this is wrong strain of flu. Not only is it relatively non fatal, it kills off those who have little impact on health costs and causes widespread morbidity, only increasing costs. Of course, the government is incompetent, so leave it to them to do it all wrong.

As the Chair of our Infection Control committee, the hospital bylaws give me, in case of emergency, the powers to do anything I damn well please to control infection, including isolating patients, shutting down hospital wings, and sending people home. And I have had the opportunity to do all the above, but never by myself. At least in the hospital we work with consensus. You don’t close a hospital wing lightly.

States have also long had the power to compel people in infectious disease emergencies. I remember, and I am sure some of you will be appalled, as a resident we had a person with cavitary (read very infectious) tuberculosis who refused medications and was homeless (and crazy). As a public health risk she was basically incarcerated in the hospital and forced to take Tb medications. It was not fun.

It is an interesting question to what extent the state will compel patients in the case of widespread contagion. Hopefully they will not respond like the Italians to bubonic plague and brick people up in their houses, presumably with a cask of amontillado. It is also the case that our legislators, generally being ignorant of things medical and scientific, will pass stupid laws. Don’t get me started in mandatory MRSA screening.

I do see the need for these laws as the history of plagues demonstrates that people do not necessarily exhibit their best behavior nor act rationally in an epidemic. Fortunately, as this strain of flu is not usually fatal, calmness will probably prevail and we will not be turning our government over to the UN, although just how this is supposed to occur logistically is never stated.

FLU WILL MELT MY IMMUNE SYSTEM

The reason I do not want to call it the swine flu, besides the fact it is not really from swine, is that it hearkens back to 1976 when we last had a ‘swine’ flu. (I want to call it the rotting genitals flu, it may make the vaccine more desirable). With that vaccine was a bump in the incidence of Guillain- Barre syndrome (GBS), as disease where the insulation of your nerves falls off, leading to paralysis.

Not a good disease. Now as I write this on 9/8/9 there have been 598 deaths from H1N1. How many cases of Guillain- Barre syndrome were there in 1978 ? 532 cases that occurred within 5 to 10 weeks of the vaccine in over 40 million vaccinations. Why? No one knows.

“As of 1976, >50 “antecedent events” had been identified in temporal relationship to GBS, events that were considered as possible factors in its cause. The list included viral infections, injections, and “being struck by lightning.” Whether or not any of the antecedents had a causal relationship to GBS was, and remains, unclear. When cases of GBS were identified among recipients of the swine flu vaccines, they were, of course, well covered by the press. Because GBS cases are always present in the population, the necessary public health questions concerning the cases among vaccine recipients were “Is the number of cases of GBS among vaccine recipients higher than would be expected? And if so, are the increased cases the result of increased surveillance or a true increase?” Leading epidemiologists debated these points, but the consensus, based on the intensified surveillance for GBS (and other conditions) in recipients of the vaccines, was that the number of cases of GBS appeared to be an excess. (ref)”

Was it the strain of flu? Was it the preparation? Subsequent flu seasons have not seen an increase in GBS. The current H1N1 is genetically distinct from the 1976 strain (ref) and there is no cross protection from the 1976 vaccine. Given the strain difference and the improved production of vaccines, there is probably no reason to worry about increased risk of GBS with this vaccine. Unfortunately we will know for sure until we have given 40 million doses.

Don’t you love the uncertainty. That’s the problem. I have to deal with uncertainties and probabilities of complex systems. I know the estimates are that for every 1000 people who get H1N1, 40 may end up in the hospital and 1 may die. With 300,000,000 Americans, that’s 30,000 deaths (standard for flu) and 120,000 in the hospital. Compare to 598 cases of GBS and 25 deaths in 1976. About as many as are trampled by cattle each year, but no one is getting rid of steak.

That’s always a problem. Maybe 800 lives are saved by airbags a year; they kill maybe 20 people a year. Numbers vary. So the greater risk is not having air bags, and like many aspects of life, it is not all or nothing. People expect vaccines to be all or nothing. 100% effective, zero risk. Humans are not good at  trying to decide what relative risk is. Odds are far greater that you will get and die from H1N1 than the odds you will die from vaccine related GBS, assuming that the vaccine has the same risk as 1976, about the same risk as being killed by your airbags.  But we will not know with certainty until this time 2010. People do not deal well with this kind of uncertainty. As Ed said, “Doctors say that Nordberg has a 50/50 chance of getting the flu, though there’s only a 10 percent chance of that.”

Public health and influenza vaccines target populations by treating individuals, trying to do the most good for the most number of people. But real effects of influenza vaccination are on populations, and the more of a population is vaccinated, the better the population does. People miss part of the point when they look at sub groups and say, well, the vaccine only helps the elderly or pregnancy women. It’s the old adage of the rising tide lifting all boats. But my sense is that people are more selfish now than they were back in the last century, being unwilling to have 2 days of a sore arm to potentially prevent spread of a disease that may kill a stranger. Besides, they were old and going to die anyway.

A NEW AND UNTESTED VACCINE IS BEING TESTED ON THE AMERICAN PUBLIC

It is new, and it is untested. As the flu vaccine is every year. Or, more appropriately, it’s the same old flu with the same old vaccine. Keeping with the car metaphor used above, we are not seeing a new form of transportation, just a new model of the same old car.

It takes about 9 month to make a flu vaccine. The first three months or so are spent deciding on what strains are to be included and if there are representative strains that grow well for vaccine production.

After the strains are chosen, it takes about 6 months to grow up large quantities of vaccine in chicken eggs. Each dose of vaccine comes from one egg. And there is only one chicken that can make all those eggs and she gets tired. Then the vaccine is purified to just the neuraminidase and hemagglutinin proteins that are in the vaccine.

The fast track we have now is due to a lucky confluence of factors. First, industry had just finished making this years seasonal flu vaccine so they had the unexpected capacity to churn out vaccine. But more importantly they had a jump on picking the strain. They did not have to guess which strains to include, they knew it was H1N1, so that gave them a three month head start. That is the main reason we have the H1N1 vaccine in record time. The process of growing the influenza and purifying it is preceding at the usual pace. We we just lucky that we were able to know the exact strain and it occurred when we had the capacity to make extra vaccine.

So while it is being produced at a faster rate, it is not because they are skimping on the steps in the production, it is because we got lucky. As an aside, I am told that the strain they are using for the vaccine is not the best at growing in chicken eggs and is a reason the vaccine will not be ready until mid October. Evidently it does not grow as robustly in chicken eggs as they would like.

As far as anyone can tell, they is nothing special about the H1N1 strain (and they have looked at it closely) to suggest there is anything unique about it except that it is immunologically new (at least since 1950′s, when the H1N1 progenitors were last seen in humans). This H1N1 in part can be traced back to the 1918 strain and explains why those over 60 have a decreased death rate rather than the usual increased mortality from influenza: old people have cross reacting antibodies to the strain that is protective.

This strain is only new to people born since about 1950, which is billions of people at risk with no immunity. But as far as virulence and antigenicity, it is the same old influenza, re-assorting its RNA to come up with new strains as it has always done and will continue to do as long as there are people pigs and birds around to get influenza.

H1N1 is fundamentally the same as any other flu that we have been making vaccine against for as long was he have been making vaccine. It is undergoing the same testing we have used every year and there is no reason to suspect that we should be doing otherwise.

I am nervous. Fall is coming. If H1N1 comes again (and pandemics have swept through the world several times in one year, the 1919 flu may have had three peaks) before the vaccine, we could be in a world of hurt. Not a lot of deaths by US standards (we lose that 30,000 or so to guns or car accidents every year, just like flu). I have spent a career watching people suffer and occasionally die of potentially preventable illnesses. I am not a fan of death by infection. I hope the vaccine is widely available and widely used so that people live to die at a later date by  “a parachute not opening… that’s a way to die. Getting caught in the gears of a combine… having your nuts bit off by a Laplander, that’s the way I wanna go!” But I digress.

Posted in: Public Health, Vaccines

Leave a Comment (21) ↓

21 thoughts on “More Flu Woo For You, Boo Boo

  1. Michelle B says:

    Not only was your post informative (I did not know about over 60 year olds having acquired immunity to H1N1), it presented humor in the silly form (one of my favorite styles). Hence along with the learning, came laughter.

  2. Sam says:

    Speaking of epidemiologic data concerning vitamin D, there’s this study.

    “To our knowledge, this is the first population-based study to evaluate and demonstrate an association between serum 25(OH)D level and [upper respiratory tract infections],” wrote lead author of the study Adit Ginde, MD from the University of Colorado, Denver. “The association seems to be robust, with a clinically and statistically significant association present in all seasons and when controlling for potential confounders.”

    According to this article vitamin D deficiency may be more widespread than previously thought.

  3. Todd W. says:

    Great article. I particularly enjoyed reading about the timeframe and process for manufacturing a flu vaccine.

  4. wertys says:

    The newsletter I get from my local homeopathic practice is very reassuring on this point. Apparently homeopaths around the globe are frantically poisoning themselves (sorry ‘proving’ remedies) to find the exact symptoms of swine flu and hence dilute up homeoprophylaxis for it. So all you sheeple who expect Big Pharma to save you may still be saved if you recant.

    BTW, is the Big Farmer the guy who owns all the vaccine chickens ?

  5. revere says:

    Couple of things. H1N1 is a subtype, not a strain (the type is A). Exactly what a strain is for a virus is a little tricky, but you could say this is a swine-origin strain of subtype A/H1N1. 1918 was H1N1 also, and was the circulating seasonal flu until 1957 when it was replaced by H2N2 which in turn was replaced in 1968 by H3N2. Up to that point only one subtype circulated at a time. Then, in 1977 H1N1 came back and started co-circulating with H3N2. It has been doing so ever since. So it isn’t accurate to say that H1N1 disappeared in 1950. Far from it. Last flu season (before the pandemic, was primarily an H1N1 flu season (human). The next one promises also to be H1N1/swine flu, a different strain of the same subtype.

    But you raise a point that is very puzzling. It’s true that those of us over 60 (I’m 67) seem to have some cross-reactivity to swine H1N1 (it’s still only about a third of us). The question is “why?” given that H1N1 has infected the population every year until 1957 and since 1977. We don’t know. But it is interesting that the 1977 return is generally regarded the result of a lab accident, either in Russia or China, probably from a vaccine plant. This was postulated and now generally accepted by one of the deans of flu lab science, Peter Palese at Mt. Sinai, because the 1977 virus was virtually identical to a 1950 isolate from a Russian lab freezer Palese had. In 1951 two H1N1 strains circulated in the world, a mild north European or Scandinavian virus, also circulating in most of the US (except New England) and a nasty fairly virulent one found in the UK and Canada and New England. In fact the mortality in Liverpool, the epicenter of the 1951 flu bad flu season in the UK, was worse than the 1918 virus. It may be that those of us who are older and do or don’t have some immunity to swine flu have it (or don’t) because of experience with one of those two H1N1 variants. That’s just speculation, though. The point is, H1N1 didn’t disappear in 1950.

  6. Kultakutri says:

    On a side note, what’s the problem with mandatory MRSA screening? I’m no expert in the field and a quick google search threw heaps of praise but, well, I know that it may only mean that the meme spread.

  7. Mark Crislip says:

    To really know if someone has MRSA you should do nose, throat, rectum, wounds and skin folds. One swab? and use it in what order?

    Or 5 swabs at 80 dollars a pop.

    If positive, then what? Data that you can make a meaningful intervention or erdadicate the organism is variable, costly, will drive resistance and is potentially toxic (and I am talking in the asymptomatic carrier).

    It also diverts resoures and it is suggested (I think wenztel, I can’t find the ref this am) that you get more bang for the buck by focusing on general infection control.

    I think, with states like Warshington mandating it I may have found the topic for a future post.

  8. Deetee says:

    Great post Mark, and some lovely analogies about risk (which I might just borrow!). This is the most difficult thing to grasp. In the UK we are being frustrated in our efforts to plan ahead because the media every few days publicise surveys among different population groups showing how few will be accepting the vaccine because they think it is too dangerous. We have had nurses (30%), then pregnant women (50%) and now doctors (50%) saying they will not be vaccinated. Things have not been helped by uninformed doctors publishing ill judged articles in the quality press (never mind the tabloids) headlined: “Just don’t try giving me the flu vaccine”
    http://www.guardian.co.uk/lifeandstyle/2009/sep/08/dr-crippen-swine-flu

    As an aside regarding MRSA our hospital screens with PCR on admission, and so we can barrier nurse positive patients. This may be only one of several infection control measures, but we have seen a big fall in MRSA that is hospital-acquired as a result. Patients are not disadvantaged and back of the envelope calculations show the savings outwiegh the costs of screening. I wasn’t a real fan, but it seems to be working.

  9. Mark Crislip says:

    mrsa screening is definitely controversial; in my own institutions we have not done screening, but have been agressive with hand heigience, basic infection control and best practice bundles and as a result have sent all out infections, inc MRSA, down. We have almost zero vaps, line infections, and our wound infection mrsa rates are lower than should be for the ammount of mrsa in the community.

    I am suspicious it is not the mrsa screening, but adherence to all things infection control, as you can have the same result without screening. I think

  10. KGelling says:

    “… flu occurs in the tropics where it is always sunny…”

    It looks like flu occurs in the tropics during rainy seasons (http://www.ncbi.nlm.nih.gov/pubmed/9623927) when it isn’t sunny.

    Can you provide some figures? How vitamin D do you need to not be deficient, how do you know if you are deficient and what level of vitamin D supplementation (or sunlight?) is needed to prevent deficiency?

  11. Sam says:

    To KGelling:
    Many of your questions are answered in this article from the Vitamin D Council website:

    Am I Vitamin D Deficient?

  12. KGelling says:

    To Sam:

    The RDA for vitamin D is 400 IU, but the link suggests taking 5,000 IU per day. Is this safe?

    Also the link suggests that a level of 50 ng/ml (of 25-hydroxyvitamin D) is required, but I’ve seen elsewhere vitamin D deficiency quoted as less than 20 ng/ml. Which is correct?

  13. Todd W. says:

    @KGelling

    According to the NIH Fact Sheet on Vitamin D, the upper intake level is 2,000 IU per day for long-term intake. Short-term intake (8 weeks) appears to be safe up to 50,000 IU/week.

    More info can be found at http://ods.od.nih.gov/factsheets/vitamind.asp

  14. wales says:

    Here’s a piece of good news about H1N1:

    “New estimates suggest that the death rate compares to a moderate year of seasonal influenza, said Dr Marc Lipsitch of Harvard University. “It’s mildest in kids. That’s one of the really good pieces of news in this pandemic,” Lipsitch told a meeting of flu experts being held by the U.S. Institute of Medicine.”

    http://www.reuters.com/article/idUSTRE58E6NZ20090916

  15. Jurjen S. says:

    Not a lot of deaths by US standards (we lose that 30,000 or so to guns or car accidents every year, just like flu).

    Actually, the number of deaths due to motor vehicle collisions is almost half again that number: something in the 40,000-45,000 range. And of the firearm deaths, over half are suicides, of whom it’s very likely they would find some other way to off themselves if they didn’t have guns available. Just to provide some added perspective.

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