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When flu strikes, why are some family members reduced to shivering wrecks under their duvets, while others get off with little more than a snuffle?
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Scientists now have an answer, showing that the generation you belong to - and even the year of your birth - predicts how vulnerable you will be to a given strain of seasonal virus.
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The flu virus a person first encounters as a child, they found, leaves a permanent "imprint" on the immune system, giving them robust protection against similar strains and much weaker protection against less closely related varieties of the illness.
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Michael Worobey, head Ecology and Evolutionary Biology at the University of Arizona and a senior author of the study, said: "It's not the age, it's the birth year that matters."
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In future, seasonal vaccines could be targeted at people of particular ages who are most likely to benefit, and in pandemics when medications are scarce, vulnerable age ranges could be prioritised for protective measures.
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"It's breaking new ground for flu, where predictions are really hard," said Worobey. "For any given potential pandemic virus, we can actually now say ... this is the age group that you can expect is going to end up in hospital dying and this is the age group who will be protected."
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The age effect is seen because influenza A viruses - the kind considered most likely to cause pandemics - have evolved into two major branches known as type 1 and type 2 flus.
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Up until 1968 all viruses in circulation belonged to the type 1 branch; between 1968 and 1979, type 2 dominated. Since then, strains belonging to both branches have been in circulation simultaneously, but with one type tending to dominate each year. "It's like an oak tree that has a trunk that splits into two major branches and 1968 becomes this really clear dividing line," said Worobey.
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Using vast databases of historical epidemiological data, the scientists tracked the susceptibility of each birth year from 1918 to the present to the different flus in circulation during their lifetime.
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The findings, published in the journal Science, showed that the strains in circulation early in life - most people have had flu by the age of five - have a profound impact on which types of flu they would be more sensitive to in the future.
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"The (first virus you encounter) seems to set you up for life to be quite good at protecting yourself, not just against that particular virus, but also close cousins of that virus," said Worobey.
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The scientists also studied two bird flu viruses, H5N1 (belonging to the type 1 branch) and H7N9 (type 2), each of which already has caused hundreds of cases of severe illness or death in humans. Scientists are concerned that in the future either of these strains could gain mutations that allow them to not only jump from birds into humans, but also spread rapidly between people, triggering a deadly pandemic.
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They found that if a person's first flu infection belonged to the same branch as the avian strain, they had a 75% reduced chance of hospitalisation and about an 85% smaller chance of dying.
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The findings explain the surprising observation that H5N1 tends to cause far more mortalities in younger people - contrary to what might be expected, while H7N9 tends to be most devastating in the elderly population.
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"We're not a completely blank slate when it comes to how susceptible we are to these emerging flu viruses," said Worobey. "Even if we've never been exposed to H5 or H7 viruses, we have some kick-ass protection against one or the other."
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This happens, he said, because when a person is infected by flu, their original antibodies are woken up as the body's first line of defence, meaning if they are poorly-matched they will be less efficient at attacking the virus.
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Previously, people had put these patterns down to younger people being more likely to encounter birds, or the virus being more aggressive in elderly people.
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The scientists said it was not yet clear whether current childhood flu vaccines - which tend to involve components from both branches - would mean in future children would have higher protection against flus of both types.
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