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An Influenza Primer

The President’s Council of Advisors on Science and Technology recently submitted its report to the president in which they stated that this influenza season might kill 30-90,000 people in the US.  This forecast of the upcoming season caught the media’s attention and appears to have stoked the public interest in influenza.  We have had many requests for more information about influenza here at SBM, and so in this post I am going to discuss the basics of influenza and try to put the current pandemic and upcoming season in perspective.

I find it is best to start at the beginning.

What Is Influenza?

Within the public sphere, “The flu” has become shorthand for “I feel like crap.”  I suspect that this is part of the reason why some people think the influenza vaccine doesn’t work.  Medically speaking, however, influenza is a very specific family of viruses that cause a reasonably narrow set of problems for humans.

The influenza season in the Northern hemisphere usually runs from October through May, with a peak mid-February.  Every season in the US between 5-20% of the US population is infected by influenza, and while the majority of people recover well from an influenza infection, not everyone will.  Annually 200,000 people are hospitalized, and on average 36,000 will die either from influenza or its complications.

The classic influenza infection incubates for 1-4 days after exposure.  Its onset is rapid, with most people experiencing high fever, headache, muscle aches, dry cough, sore throat, and nasal congestion.  Gastro-intestinal symptoms like nausea, vomiting, and diarrhea are less common.  Symptoms last from several days to almost two weeks, and a person is contagious from one day before symptoms begin to more than a week after symptom onset.

There are many strains of influenza. The current seasonal influenza is made up of three different influenza subtypes: A(H3N2), A(H1N1), and B.  Don’t confuse the seasonal A(H1N1) strain with the current pandemic 2009 A(H1N1); they are distinct.  I will refer to them as A(H1N1) for the seasonal strain, and 2009 (H1N1) for the pandemic “swine flu” strain.  Influenza B is less common, less virulent, has a slower mutation rate, and is thus a lesser risk; the rest of this discussion is focused on Influenza A.

How Does Influenza Spread?

Influenza has two dominant modes of transmission: droplet and contact transmission. Droplet means that when someone coughs or sneezes, extremely fine (and sometimes not-so-fine) droplets are aerosolized into the air around them.  If these droplets come in contact with your nose, mouth, throat, or lungs, it is possible for you to become infected by the viruses in those droplets.

The second way influenza can be spread is either through direct contact or through an intermediate like a doorknob, known as a “fomite.”  The virus can survive for minutes to days depending on the surface, and if you touch that surface then your mouth or nose, again, it is possible that you can become infected.  Influenza does not appear to be capable of spreading long distances through the air (across large rooms or through air vents).

How Does Influenza Change?

Influenza A is a versatile virus with many distinct serotypes.  Most people are familiar with human, bird, and swine influenza, but influenza is in fact able to infect a large number of avian and mammalian species on the planet.  It is important to realize that these viruses are not, despite their name, truly species specific. Random mutations and natural selection frequently create new strains of influenza capable of infecting other species; in its ability to mutate influenza is unparalleled.

Influenza is an RNA virus encoded by just 11 genes on 8 separate RNA segments.  With only 11 genes, you can see that influenza is a relatively simple virus.  But its simplicity is one of the most significant reasons for its success.  Unlike our DNA, the RNA of influenza replicates without the benefit of enzymes that correct transcription errors.  This means that it makes more transcription errors, a lot more.  One in every 1000-10,000 nucleotides is mis-transcribed by influenza, giving it one of the highest mutation rates known.  Some of these errors are neutral and have no effect on the virus.  Some are detrimental and will result in a defective virus.  But some of them are beneficial.  Two genes encode influenza’s characteristic surface proteins hemagglutinin (HA) and neuraminidase (NA).  There are 16 types of HA, 9 of NA, and respectively these two proteins serve to bind the virus to a target cell and to release new viral particles from a host cell, and they also happen to be the parts of influenza the immune system recognizes.  Every so often a transcription error will change the conformation of either HA or NA just enough so that it cannot be recognized by the immune system.  Voilà, we have a new strain of influenza, and your immune system has to start from scratch.  This is the concept of “antigenic drift,” and it is responsible for the variation in influenza strains we see every year.

But that is only part of the story.  Do you remember the 8 separate RNA segments?  If a cell is infected with a single strain of influenza this is an inconsequential factoid.  However, if two dissimilar strains of influenza co-infect the same cell, those 8 RNA segments become exceedingly important.  Up to 256 unique combinations can result from that one pairing.  Instead of a slow drift in the surface markers of the circulating influenza strains, suddenly we have a major re-assortment, and a brand-new strain is created.  This is “antigenic shift,” and this is how the 2009 (H1N1) strain was born.

I hope it is clear at this point that influenza is not a single virus that changes over time, but is instead a family of viruses that to a greater or lesser extent co-exist and are constantly changing.  Were it stable, your immune system would be able to establish meaningful immunity.  Until we discover a way to make your immune system target a stable section of influenza, our best hope is to constantly redesign our vaccines against a moving target.

What Makes the Novel Influenza A 2009 (H1N1) So Special?

Other novel influenzas have been identified in the past without causing a pandemic.  The 1976 swine flu is a prime example.  Identified in Fort Dix, it infected at least 13 soldiers, killing one.  It looked similar to the 1918 Spanish flu, which raised concerns of a potential pandemic and triggered a mass vaccination campaign. Yet it never spread beyond the base and has not been seen since.

Another example is the H5N1 “bird flu” that we’ve heard about since its emergence in 1997.  It has had several outbreaks, caused over 167 deaths, and carries a ~60% mortality rate for those infected.  Fortunately, though it can spread like wildfire through birds, and humans can catch it from birds, humans cannot reliably spread it to other humans.  Thus it is a virus with the potential to be truly terrifying, but in its current state poses a limited infectious risk.

Why then are we so confident that the 2009 (H1N1) strain will behave differently and pose a real risk? Three reasons:

First, recall that the 2009 (H1N1) is distinct from the seasonal A (H1N1).  It appears to be a “triple recombination,” with characteristics derived from human, bird, and swine influenzas.  When our population was tested for antibodies against 2009 (H1N1) nearly no children, and less than 10% of those under the age of 65 had reactive antibodies, and of those over 65 only 33% showed any response.  It seems no one has seen a similar influenza in half a century.  This means that the vast majority of our population is susceptible to infection this season; you can see the potential for infection on a grand scale.

Second, unlike the 1976 strain, the 2009 (H1N1) has already proven itself to be highly contagious.  From its first appearance in Mexico on March 18th, 2009, it took 4 weeks to spread outside the borders of Mexico, and within 2 more weeks it was in 5 states and 8 other nations. Only 6 weeks after being first identified, over 3000 cases were to be found in 43 states and 23 countries, and on June 11th, 2009, after only 3 months, it had achieved pandemic status.  Furthermore, it was able to accomplish all this during the season least conducive to its normal spread.

Finally, the 2009 (H1N1) has proven itself to be far from benign.  As of August 22nd, the US has hospitalized 8,843 people with 2009 (H1N1), and 556 have died, 101 of them under the age of 24.  We have a hospitalization rate of 4.5/100,000 for ages 0-4, and 2.1/100,000 for ages 5-24.  All of this, recall, has happened during influenza’s off-season.

In areas where 2009 (H1N1) emerged during the traditional influenza season, like Australia, they have reported more than a doubling in the number of people hospitalized from influenza, with around 1 in 5 requiring ICU-level care.  Similar to what we have seen in the US, Australia has likewise demonstrated that 2009 (H1N1) has a higher attack rate in younger people, which is in stark contrast to the normal seasonal influenza pattern, and has shifted its mean age of death from influenza from 83 down to 54.  Unlike what we have seen thus far, Australia has had a much higher hospitalization rate of 34.6/100,000 in ages 0-4, and an overall rate of 12/100,000 for the population.  This likely reflects the differences between being on-season and off-season.

That is what makes 2009 (H1N1) so concerning.  It is capable of causing serious infections even and perhaps especially in the young and the healthy.  It is highly contagious, it has a worldwide population without immunity, and it now exists in low levels in most communities around the nation.  And we are now entering into its prime season.

Conclusion

So is this the Zombie Apocalypse, or only slightly less concerning, is this going to be a repeat of the 1918 Spanish influenza pandemic? Almost certainly not.  Nor, however, were the predictions made by the President’s Council of Advisors on Science and Technology outlandish fear mongering.  30,000 dead is an average influenza season, and if we see a simple doubling in the number of cases we will rapidly approach the higher end of their estimate.

Influenza warrants our respect and attention.  I hope these estimates are higher than what we will in reality see; it would make my winter in the ICU far more pleasant.  The fact remains that only time will tell.  In the meantime, we would be wise to be prepared.

So what can you do?

  • Get vaccinated against seasonal flu and 2009 (H1N1) – It’s cheap, safe, and effective. If you don’t get sick, you avoid all of the risks of infection while also avoiding the responsibility of infecting others.
  • Wash your hands – You should be doing this anyway.
  • Cover your cough and sneeze – It’s just polite not to spray your mucous in my face.  Thank you.
  • If you are ill stay home until 24 hours after your fever abates – If you are infected, there is no reason to risk the health of everyone around you.
  • Don’t Panic – Most people will get through an influenza infection without medical attention.  Rest, stay hydrated, and minimize your exposure to others.

The CDC recommendations for warning signs to seek medical care are as follows:

In children, emergency warning signs that need urgent medical attention include:

  • Fast breathing or trouble breathing
  • Bluish or gray skin color
  • Not drinking enough fluids
  • Severe or persistent vomiting
  • Not waking up or not interacting
  • Being so irritable that the child does not want to be held
  • Flu-like symptoms improve but then return with fever and worse cough
  • Any child under 12 weeks of age with fever over 100.4 F (38 C)

In adults, emergency warning signs that need urgent medical attention include:

  • Difficulty breathing or shortness of breath
  • Pain or pressure in the chest or abdomen
  • Sudden dizziness
  • Confusion
  • Severe or persistent vomiting
  • Flu-like symptoms improve but then return with fever and worse cough

Posted in: Public Health, Science and Medicine, Vaccines

Leave a Comment (40) ↓

40 thoughts on “An Influenza Primer

  1. woo-fu says:

    Thank you for this update. Does the CDC mention at what temperature adults should seek medical intervention? Two nurses I spoke with said 102; is this correct? And is this while on or off NSAIDs?

    I would just like to add a few additional comments regarding school and work:

    Many parents utilize schools as the primary caretakers of their children while they are at work, having to scramble to obtain care or get off from work if they find their children might be ill. This situation has, for generations, prompted parents to send their children to school unless they were in truly dire straights.

    But ignoring the early warning signs not only puts their child at risk, but the entire school population* and their families. Parents must have back up plans if/when they need to keep their children home. They must not wait until the last minute.

    The same can be said of the workplace. When I was growing up, toughing it out was considered noble. Taking sick days when a person didn’t need to be hospitalized was the subject of scorn. But it is not noble to tough it out; it is irresponsible. And any employer who does not yet understand this is even more irresponsible.

    *Sadly, this is a major problem for teachers, too. Many schools do not allow a generous enough budget to retain a sufficient pool of substitute teachers, creating great pressure for teachers to report to work ill, compounding the problems for schools.

    Again, thanks for the info.

  2. woo-fu says:

    Regarding my prior comment: that should be “dire straits.” I’m running a fever myself this morning. Fortunately, I’m staying home and away from others.

  3. qetzal says:

    Excellent primer. Thanks!

    Does anyone know why influenza is seasonal? Also, is it just infection rates that increase “in season,” or does severity increase in season as well?

  4. Dacks says:

    Great summary of what influenza is, and who is susceptible.

    Would it be possible to follow this up with a “vaccine myths and facts” article? There is a lot of misinformation among the general public, such as:

    - The swine flu vaccine is a very new vaccine, and is being tested on children
    - People can get the flu from the vaccine
    - “Boosting your immune system” is the best way to avoid getting the flu

    I have heard this from three different nurses in the past week. It worries me that nurses are refusing to get the vaccine, and are scaring parents away from vaccinating their children. A short primer would be very useful in rebutting these myths.

  5. Calli Arcale says:

    qetzal — I seem to recall reading something about influenza being cold-adapted. It’s actually evolved insulation. Conventional wisdom was that people are just more cooped up in the winter, and thus can more easily spread stuff, but (IIRC) it turns out that it actually physically transmits more easily when the air temperature is lower, totally apart from how many people are stuck together in the same cube farm or whatever. But it was a while ago that I read that, so I don’t have a link and may be misremembering details.

  6. Peter Lipson says:

    Well done, Doc, thanks!

  7. Todd W. says:

    Wonderful article, Dr. Albietz! I particularly liked how you explained the difference between 2009 (H1N1) and the 1976 swine flu.

    Cover your cough and sneeze – It’s just polite not to spray your mucous in my face. Thank you.

    I would just add to this: cover your cough and sneeze with a tissue or your sleeve, not your hand. And if you use a tissue, wash your hands afterward.

    There’s not much I hate more than when a person coughs or sneezes into their hand, then grabs something, like the bar/strap on the subway.

  8. qetzal says:

    Thanks Calli.

    I found an interesting 2007 paper on the subject here. It presents evidence that flu strains migrate globally, from Northern Hemisphere to Southern and vice versa.

    In the discussion, the authors say that the cause of seasonality is not understood, especially since seasonality is only observed in temperate lattitudes (in both hemispheres). In tropical areas, flu apparently infects people equally year round.

  9. qetzal says:

    Sorry to double post, but I found a 2009 PNAS paper that gives fairly good evidence to suggest seasonality may be caused by absolute humidity. They reanalyze some pubished data from other studies and show that influenza virus survival is strongly, inversely, and non-linearly correlated with absolute humidity (vapor pressure).

    Interestingly, the correlation to absolute humidity (AH) is much stronger than to relative humidity (RH). Also, during winter months, RH decreases indoors, but increases outdoors. In contrast, AH decreases both indoors and outdoors in winter.

    The authors are careful to note that this is just a hypothesis that needs further testing, but it sounds pretty plausible.

  10. Newcoaster says:

    Great refresher on influenza for those of us struggling to recall Med 1 Infectious Disease, and more clearly written than most of the government memos that have come my way on this looming threat.

    Another group of people particularly hard hit by H1N1 are aboriginals, with a scarily high rate of ventilated young natives in Manitoba this past summer. http://www.cbc.ca/canada/manitoba/story/2009/09/03/mb-swine-flu-winnipeg-kumar.html

    Regarding nurses not getting vaccinated. I certainly have run across this behaviour in nurses myself…especially those who work in ER/ICU. I don’t know where this attitude comes from, the claim that “I got the flu from the flu shot”.

    Superstitious beliefs and sCAM practices are certainly much more common in nurses than physicians, in my experience. I am always running across nurses who claim the ER is busier on a full moon, who get very upset if I say “it’s pretty quiet in the ER today” because that will cause a influx of sick people, and it is mostly nurses who practice the woo-woo Therapeutic Touch.

    I suspect it is because their training is less in depth, or science based than for physicians, and they are mostly learning procedures and algorithms rather than broader concepts which helps us know when to ignore the algorithms and practice guidelines.

  11. Joseph Albietz says:

    Dacks – Thanks! At least one influenza vaccine myths and facts article is in the works.

  12. Joseph Albietz says:

    Thank you all for the kind words; I’m glad you’ve found this helpful!

    Regarding influenza vaccine refusal, I wouldn’t single out nurses; health care workers in general have not done a good job getting vaccinated.

    http://www.cdc.gov/mmwr/preview/mmwrhtml/rr58e0724a1.htm#tab3

    Table 3 shows the percentage vaccinated of various groups over the last three influenza seasons. Only ~ 40-45% of HCWs have been vaccinated the last few years. Most of the other high-risk groups are similarly abysmally low.

    Beyond the fact that HCWs have a higher risk of exposure and of contracting influenza themselves, HCWs have, in my opinion, a professional responsibility to not place their patients at risk by allowing themselves to become infected.

    This season my hospital is providing free influenza vaccinations for all employees, and is not accepting non-medical influenza vaccine refusals from employees. If an employee does refuse a vaccine, they are to be required to wear an N-95 mask at all times when caring for patients. This is an imperfect solution to be sure, but it is better than the stances we have had in the past, and I hope that the social and professional pressure (not to mention the discomfort of wearing an N-95 for 12+ hours) will improve our HCW influenza vaccination rates this season.

  13. Peter Lipson says:

    We HCWs also have an ethical responsibility to avoid this illness during a pandemic so that we may care for those who are struck down. During non-pandemic years, the argument is weaker, but at a time when our capacity may be strained, we need as many of us as possible at work and healthy.

  14. DVMKurmes says:

    Calli Arcale has a good memory- here is a link with the references;

    http://www.enotalone.com/article/19327.html

    Absolute humidity levels actually affect flu virus survival-higher humidity kills them, so the low absolute humidity that is an effect of colder air allows flu viruses to survive much longer in the environment.

  15. MOI says:

    I am pregnant. I hear that preggos are high on the list to get vaxed for H1N1. Will somebody please ease my fears regarding this vaccine? I know other pro-vax moms that are avoiding this vax because it’s thought to be “new” and “not tested on pregnant women”.
    Is there any real difference between this vax and the other flu vaxes? Would those differences pose a risk of injury? I have no problem getting the other flu vaxes but I just don’t know enough about this one to make a decision that I’m comfortable with.

  16. Harriet Hall says:

    MOI,

    We have more than one article coming up on the blog in the near future to address myths about the new vaccines. Meanwhile, I’ll just say that if we waited for the vaccine to be no longer new and to be fully tested on pregnant women, it would be too late for it to do any good. No, there is no reason to think this is any more dangerous than the usual annual flu vaccines. And we know swine flu is particularly dangerous to pregnant women. If I were pregnant, I would be first in line.

  17. MOI says:

    Thank you Harriet! I’ll be looking forward to those future articles and will be pointing many anxious pregnant ladies to those articles.

  18. Deetee says:

    I’ve recently done a post on swine flu vaccine and reactions like Guillain-Barre if you are interested:
    http://layscience.net/node/625

    I’m looking forward to reading Harriet’s post about vaccine myths.

  19. Deetee says:

    Regarding the pregnancy issue….
    It seems that 5-10% of the deaths so far have been in pregnant women, who only make up around 1% of the population.
    The hospitalisation rate is 4x the usual if you are pregnant.
    Miscarriage is also a risk from the high fever that can occur.

    These all seem to me like excellent reasons to get immunised if you are pregnant.

  20. TsuDhoNimh says:

    MOI –
    http://www.aafp.org/online/en/home/publications/news/news-now/clinical-care-research/20090826h1n1vacc-trials.html

    “Trials involving pregnant women are scheduled to begin in early September”. They waited until the non-pregnant adult trials showed no problems.

    I got my seasonal flu shot AND my pneumovax today, so I feel like crap with two sore arms and a fever, but like Peter Lipson said … we have an obligation to stay healthy and not spread the disease.

  21. I saw a woo pusher citing the study “Prevention of influenza episodes with colostrum compared with vaccination in healthy and high-risk cardiovascular subjects: the epidemiologic study in San Valentino.” by Cesarone et al. (http://www.ncbi.nlm.nih.gov/pubmed/17456621?dopt=Abstract) to claim that not only is the flu vaccine is ineffective, but that colostrum was much more beneficial. The CAM community is apparently embracing this in dissuading people from taking the flu vaccine. Is there an expert in contagious diseases or virology on here that can help analyze this study?

  22. Calli Arcale says:

    Yay! I rememberd something correctly! Always nice when that happens. Thanks, guys, for finding the links!

    Jason, I’m no expert (I’m a software engineer), but it doesn’t seem reasonable that colostrum would protect better. Three reasons come to mind:

    1) The modest protection offered by colostrum comes in the form of maternal antibodies. If the mother has never been exposed to the virus (and this is a new virus, so odds are extremely good she hasn’t), her colostrum will have no protection against this new strain of H1N1 influenza — unless, of course, she has been vaccinated against it.

    2) Colostrum doesn’t confer any immunity. It just has antibodies and stuff. Once those are expended or decayed, there is no protection whatsoever. I’m not sure what the “half life” of maternal antibodies are, but without the maternal lymph nodes to make more, I can’t imagine this would last long.

    3) Colostrum is produced only in the first few days after birth; after that, the mother’s milk comes in and replaces it. (And boy, do you notice it when that happens!) So newborns only get very short-term protection from colostrum.

    Bottom line: since newborns can’t tolerate the flu shot, they shouldn’t get it. Thus, colostrum is really their only defense — that, and not being exposed to carriers, which means that the best thing to do if you’re going to have a baby during flu season is to get vaccinated — and get everybody else in your family vaccinated too, so they don’t pass it on to your child.

  23. gmrath says:

    NPR had a segment on 2009 N1H1 this afternoon and I gather from that broadcast the 2009 N1H1 vaccine is not “NEW” in the sense that it’s based on new technology and/or production methods, but is in fact produced the using the same methods as seasonal influenza vaccines produced for years. Also mentioned is these vaccines do not contain adjuvants.

    Finally the reporter pointed out that at least 6 Big Pharmas are currently making both 2009 N1H1 and seasonal influenza vaccines. Wasn’t it a few seasons ago the only domestic producer of influenza vaccines had to shut down for six weeks as a result of production line contamination issues?

  24. MOI says:

    DeeTee – Thank you! Your article was just what I was looking for!

    TsuDhoNimh – And thank you for providing that information. =)

  25. Juan Antonio says:

    Thanks for this excellent primer on influenza! I took the liberty to translate it into Spanish, adding some brief notes to put the information in the context of Mexico, and posted it on my blog.

    http://navarroj.blogspot.com/2009/09/preparados-para-la-influenza.html

    I think this is really important to understand what the virus is, and how to be better prepared for this following flu season.

  26. k7aay says:

    Why is flu more ferocious in the winter?
    One possible reason: Lower Vitamin D levels due to lower exposure to sunshine = lower immune function. See http://www.grassrootshealth.net (a project of the UCSD Med School) for details. Then, ask your doc to test your blood level for Vitamin D.

  27. Todd W. says:

    @k7aay

    That idea doesn’t really hold up, since flu is a year-round thing in equatorial regions, where people get greater amounts of sun and, thus, vitamin D.

    IIRC, the seasonal aspect has more to do with humidity.

  28. Y2D2 says:

    MOI -

    If I was pregnant (again) you would have to drag me kicking and screaming, at gunpoint to get me to take that vaccine.

    Anyone can type the words “it is safe” – typing words do not make them factual.

    30 days or less of testing on pregnant women – how can they ethically “test” such which contains thimersol in most cases (a mercury-based preservative) on a pregnant woman? – 30 days is supposed to be re-assuring? (Even if that was supposed to refer to September of last year – that is *hardly* enough time for me to feel reassured.)

    They have had drugs on the market for several years “approved” and stated as “safe” before they “discovered” they were potentially lethal.

    *Please* do your research from MANY sources before you make this decision.

    Best wishes to you & your new little one.

  29. deniseibase says:

    Y2D2 and MOI –

    Y2D2, how long do you think testing should go on? Is it okay to allow pregnant women to die at rates about 4 times higher than the rest of the population for any longer than necessary?

    The basic process by which the swine flu vaccine is made is well-tested, it is the same basic process we use for seasonal flu manufacture. If you feel safe getting a seasonal flu shot, you should feel safe getting a swine flu shot.

    The specific virus that causes the 2009 swine flu did not exist (at least, not that anyone knew about) before March 18th. Given that you can’t create a new vaccine overnight, being able to test it by September seems pretty darned speedy to me. It would be impossible to have tested it for longer. And before you try to argue it was too speedy & therefore sloppy, remember this is the same basic process the vaccine manufacturers use every year to quickly create the seasonal flu vaccine. Only the specifics of the virus changed – and remember too, the manufacturers are used to that also, as seasonal flu vaccine changes every year also.

    I am not pregnant, but I have two kids and I work in a natural food store. I have people ask me every single day what to do about this issue and this is what I tell them – You betcha I’m going to get the vaccine for my kids as soon as it is available for them and for myself if it becomes available for me as a healthy adult. I even make a point of bringing up the issue to pregnant women because there is so much misinformation out there and the bottom line is this – if you’re pregnant, why in the world would you do ANYTHING that would quadruple your risk of dying or killing your baby?

    So, MOI, yes, do your research from many sources before you make your decision. And then research the credibility of your sources. I think you’ll find that the most credible sources agree – you should be first in line to get the vaccine.

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