Epidemiology of Influenza subtypes

Historic prevalence of various influenza subtypes

Here at YCPMicro, we are moving steadily into the 2011-12 seasonal influenza epidemic. Currently (5 November 2011), Pennsylvania is experiencing ‘sporadic’ influenza levels, but these are expected to reach widespread levels by late December to early January.  During the 2009-10 seasonal influenza outbreak, epidemiologists were actually much more concerned about the so-called ‘swine-flu’ outbreak, which was in fact different from the predicted seasonal influenza variety. The name ‘swine-flu’ is somewhat deceptive, in that the virus is actually not particularly able to jump from pig to human. The name ‘swine-flu’ actually refers to the origin of the virus; it was a variety on influenza found in pig populations, and a random variant acquired the ability to jump into human populations. This variant then was very much able to infect humans, so it is much more appropriately referred to as ‘human-flu, originally from a pig’. Scientists were particularly worried about this outbreak, because the virus had many of the characteristics shared with the flu variant responsible for the 1918 Influenza pandemic that killed upwards of 100 million people, or about one in 20 people. 

A new commentary published in mBio, the open access journal of the American Society of Microbiology, presents a hypothesis as to why season influenza outbreaks are transient. The authors from Mount Sinai School of Medicine in New York note that pandemic influenza emerges in human populations with some regularity, and that these outbreaks are coupled with the disappearance of seasonal variant, and they propose a hypothesis as to why this might occur.

Seasonal influenza vaccines typically are only effective for that year’s most prevalent influenza subtype, and offer little protection for subtypes that emerge in the future. However, unless an individual is in one of the high risk groups (children, the elderly, or the immunocompromised), many cases of seasonal influenza can be subclinical or only cause mild signs and symptoms in otherwise healthy individuals. Consequently, when coupled with a good level of vaccination compliance, seasonal influenza outbreaks typically  burn themselves out as the population becomes essentially completely immune either due to vaccination or by being exposed to the virus.

Influenza antigens of hemagglutinin

What was noticed in 2009 was that the seasonal influenza outbreak was extremely minor in comparison to the more significant H1N1 ‘swine-flu’ outbreak, and that isolates from the ‘seasonal’ outbreak disappeared much more quickly than typical. The authors conjecture that pre-existing immunity in individuals exposed to earlier H1N1 outbreaks (primarily from 1957 and 1977) offered a degree of partial immunity mediated by B lymphocytes. The immunity was against antigens in conserved regions of viral proteins such as hemagglutinin, diagrammed here. The hemagglutinin antigen (the “H” part of H1N1) is variable from flu isolate to isolate, however immunity to the conserved stalk region can confer partial protection. Antibodies against these conserved regions further reduced the spread of the less virulent seasonal virus. Infection and spread occurs most prevalently in the more virulent pandemic variety than the seasonal variety, consequently the season variant quickly dies out due to inability to infect hosts.

The authors postulate for the future as novel influenza subtypes are generated in animal reservoirs that emergence of new pandemic influenza will rapidly displace seasonal variants if they are somewhat related, due to cross-reactivity of antibodies directed against conserved regions of viral antigens. If an emergent pandemic influenza subtype is very different from existing seasonal varieties, they may co-exist with the seasonal varieties without causing them to die out, such as what happened in the 1977 H1N1 outbreak, which was marked by a non-H1N1 seasonal influenza variety.

BONUS: The interaction between influenza virus and the human host is extremely complicated, and it is unlikely that we will ever eradicate pandemic influenza as a malady of humanity. Describe a reason why this is so. Remember: no repeats allowed! Offer good through the next exam, 16 Nov. 2011. 

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About ycpmicro

My name is David Singleton, and I am an Associate Professor of Microbiology at York College of Pennsylvania. My main course is BIO230, a course taken by allied-health students at YCP. Views on this site are my own.

Posted on November 7, 2011, in Bonus!, Danger danger danger! and tagged , , . Bookmark the permalink. 20 Comments.

  1. One reason is that a fully effective vaccine cannot be developed until the virus strain it must protect against has evolved and been identified. And once developed, there must be the production capacity to manufacture enough vaccine to protect the population. This is because the virus strain is evolving and there is no way we can know how it has evolved until it has effected the population.

  2. Point of order here: all viruses (and all living systems) have the capacity for evolution, so what you are describing is not really ‘evolution’ per se, but variation due to mutation. Evolution is the change in species over time, and results in genetically distinct populations. Influenza subtypes are genetically distinct, but genetic segments between the subtypes can be freely exchanged between them; this is actually the phenomenon that is a significant reason for why influenza will likely not ever be eradicated.

  3. In a previous viral disease called dengue fever, the immune response is primed by previous infection. When a secondary infection with other serotype is introduced it may lead to a severe disease. The antibody from the previous infection might be cross reactive by causing antibody dependent enhancement, which facilitates entry of the virus into the cells, instead of neutralizing the virus like it is supposed to. This can lead to more severe disease and might happen in severe cases of H1N1 influenza.

    • The article I summarized actually demonstrates that previous infection can modulate or diminish ongoing seasonal influenza, not the other way around. My quick Pubmed search turned up two relevant articles, both of which appear to be case study reports from areas where Dengue is endemic (i.e. the Tropics). I suspect that coinfection does not pose too significant a reason for promoting pandemic influenza.

      • Not sure if this is much different, but this same source also says a person with an impaired immunity and has repeated infection with other H1N1 virus, causes a boost in the innate immune response to increase the up regulation of cytokines and chemokines. This increase in up regulation occurred in patients with H5N1, SARS, and H1N1 during the influenza pandemic in 1918-19. Although previous infection could be beneficial, repeated infection can cause a continuous activation of the innate immune system leading to harmful effects and auto-reactivity. Could potentially happen in severe and fatal pandemic influenza cases and the reactivity of previous infection with new influenza virus is unknown and would be unpreventable until further studied.

  4. We will never experience influenza as a pandemic in our day and time because of our understanding of vaccines. Since many people receive vaccines every season to protect against influenza, the sickness is not spread as readily as it was in 1918. Vaccines work to control the spreading of a sickness in a certain area. If someone is vaccinated against influenza, they will not get it when introduced to the virus, and will not pass it on to someone around them.. therefore creating herd immunity.
    So, the more people that get vaccinated against influenza every year will decrease the likelihood of creating a pandemic.

    • The vaccines this year will be ineffective at stopping the next pandemic. When it comes out on DVD, everyone should spend 2 hours and watch the movie Contagion. We should not phrase our worries about pandemic influenza by saying “IF” but instead should be saying “WHEN.”

      Pandemic influenza IS going to happen, it’s only a question of whether hundreds of thousands of people die (annual death toll due to seasonal flu) or hundreds of millions.

  5. One reason this cannot be eradicated is because of the mutation of the viruses. In some cases an existing form of influenza can reassort with another influenza virus to create a hybrid of the two viruses. In this case a new strain of influenza virus is created and must be treated differently then the previous cases.

  6. I know you mentioned mutation and evolution of the flu virus but the best answer at what makes influenza hard to eradicate is the fact that the flu virus is made up 8 different genomes and each time you are infected with a specific strain of flu virus your body can send out defenses to fight that virus and you can get better. But then next time you could be infected with another strain of virus and then the same process occurs. This is because this virus has so many different genomes it is able to create varying strains and thus makes it dangerous and unable to eradicate because scientists would have to create vaccines for each type of possible strain. Also talking from a more worldly perspective the areas in there are more people and maybe the flu vaccine isn’t as much in demand or available or maybe there isn’t a lot of medical supplies or clean water can be festering with influenza strains spreading from person to person and since new strains of influenza are made all the time if a foreign strand is made in a crowded poverty level country then pandemic can occur and spread very easily to create an epidemic. Which then means that scientists will have to scramble to detect the strain of virus infecting everyone and make a vaccine for it. But in the mean time people will die mostly the elderly and children. And then this could repeat many times over

    • Just to clarify; each virus only has ONE genome that has a number of variable regions within that genome. The main regions of variability are in the Hemagglutinin (the H from H1N1) and Neuraminidase (the N from H1N1) genes, which encode viral surface proteins essential for the infection process. The variable regions in the head part of the virus (in the picture at the top of this posting) are the most antigenic, and are the parts that generate the strongest immune response when challenged with the seasonal vaccine. Unfortunately, these two genes are the part that change from year to year.

      Scientists are actually pretty good at predicting what varieties of seasonal influenza pop up each year, and each seasonal vaccine offers excellent protection when administered promptly. It is the pandemic influenza that is much more difficult to predict, as other variations can increase its virulence.

      Also, water supplies are not reservoirs for influenza virus; the only reservoirs are animals (birds and mammals), and the virus can only survive transiently outside of a warm blooded host.

  7. It is impossible to predict the influenza that will be occurring in the future. It is not cost efficient to vaccinate an entire population for every strain of every influenza. Only the top estimated influenzas will be vaccinated again, luckily scientists are usually correct. If the vaccinations are wrong, the population will be infected. The vaccinations also only work for a limited time. Once the time period for the vaccination runs out the person will be exposed to the influenza once again. It is just a matter of time before someone guesses wrong in vaccinating against influenza and an outbreak occurs.

    • I don’t think that it’s a matter of guessing wrong; we are doing a good job so far of anticipating which strains of influenza are most prevalent. This is of course accomplished by disease surveillance by organizations such as the CDC and the WHO, who monitor where outbreaks occur.

  8. Allison Mazzotta

    It is unlikely that we will ever eradicate pandemic influenza because of the different types of influenza. For example, Avian influenza now has the potential to cause a human flu pandemic. This is a problem because humans have not yet been infected by this type of influenza, and therefore do not have immunity to this strain. The surface proteins are different enough that humans may not develop an immune response against it, which makes this especially dangerous because the virus will not be recognized by the immune system or protect the body against the virus.

  9. It is unlikely that we will ever eradicate pandemic influenza because the speed at which new strains develop because of antigen drift is much too rapid. In result of this, it leaves a person susceptible to a new infection. With the mutations of the antibody-binding sites, due to this “shift,” it makes it extremely difficult if not impossible for antibodies to inhibit the viruses. This process is occurring in a large percentage of the population, therefore the ability to combat it is a very unlikely possibility.

  10. Pandemic influenza will never be eradicated due to the constant use of vaccines made for each form of influenza that has occured already. As we learned in class mutation is what allows for resistance; therefore after the drug sensitive cells are killed off the mutants are left and will continue to grow as stronger and more resistant cells. Also, due to the virus being pandemic most will have no immunity to the strongly resistant viral cells. On top of that, the scientists are incapable of creating a vaccine without seeing the actual influenza virus itself, which means people will have to be infected before any vaccines can come into play. There is no preventing pandemic influenza and in my opinion each time there is a pandemic outbreak, the virus will be stronger than the last.

  11. Because there are new strains of influenza forming it is hard to tell when the next flu pandemic will occur, and it will occur! The next flu pandemic will obviously not be the seasonal flu because so many Americans are vaccinated and the ones that aren’t are getting herd immunity. The vaccines that we have now only work against their specific strains, therefore, no new vaccine will work on a different strain because we can not predict them. Although no pandemics can be predicted, scientists are closely watching the H5N1 Avian (bird) Influenza. Even though the virus is just passed between birds, we don’t know if or when it could be passed on to humans. Because we really don’t know, this could easily start a pandemic.

  12. The human body has little to no immunity against pandemic influenza because it is new and different. Most people get the ordinary flu shot to protect themselves from contracting the seasonal flu virus but it will not protect you in a pandemic situation because it is a very different viral strain that takes months to identify and prepare a vaccine for. This gives the virus plenty of time to spread which it does rapidly. The main form of contraction is via respiration since viruses could be around us in the air we are breathing. The viruses can come from anywhere and are constantly adapting making protection difficult because you can’t make a vaccine without knowing what the virus is. Antiviral medicines can only help people that are already ill with the pandemic rather than protecting people from ever getting it. It could start in an animal species and morph and transfer into a human host where it then rapidly spreads. Moreover, the flu virus can survive in the guts of healthy birds which can be a threat to humans because they have the ability to turn into life-threatening pathogens. Since we can’t prevent pandemics we must learn how we can try to protect ourselves should we come in contact with them. Do this by leading a healthy lifestyle as well as good hygiene.

  13. We are not able to predict when the next pandemic influenza outbreak will occur, so we are also not able to prepare for this outbreak. It will never be eradicated because we are not able to vaccinate every person in the world. So, as long as there are unvaccinated individuals the disease can persist and spread.

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