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In 1918 through 1920, an Influenza pandemic colloquially named the "Spanish Flu", ravaged the world. It infected about half a billion people, and killed as many as 50 million people. But my question is - how did the 1918 flu virus disappear in 1920?

One can hardly believe that after infecting half a billion people, the virus was contained in any sense of the word. Why didn't the more than one billion uninfected people get infected? Why didn't we see some small epidemics continue to circulate the globe infecting the yet-uninfected as well as newly born people for many years - potentially until today?

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    $\begingroup$ What research have you done on the epidemiology of flu virus infections, before posting here? The Spanish flu was no different in that respect from the Asian Flu of the 50s, or last year’s flu strain. (Some would say that epidemiology is off-topic here, as it is some distance from biological mechanisms, but if you ask questions here you need to demonstrate that you have researched them first. ) $\endgroup$
    – David
    Commented Feb 16, 2020 at 21:32
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    $\begingroup$ I tried to see if there was any similar question on this site, and found none. I tried to Google a bit and didn't find any answer. I thought that even if an answer could be found on the Web, it wasn't obvious (at least to me) how, and it would be useful to have an answer here, on this site, for posterity. If "epidemiology is off-topic here", were is it not offtopic? Please note that I wasn't asking why the Spanish Flu is no longer a pandemic. I was asking why it went completely extinct. Is there something in the flu virus which makes it a particularly bad surviver compared to other viruses? $\endgroup$ Commented Feb 16, 2020 at 21:45
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    $\begingroup$ Another clarification: I know there is no reason why the Spanish Flu had to remain particularly common. It could remain one of hundreds different viruses going around - flus, "common colds" and so on, and reach a few people here and there. But the particular 1918 strain was very visible - it killed a large percentage of people infected. If this virus was still extant, wouldn't we see small deadly flu epidemics in various places over the last 100 years? What in the flu virus or the circumstances allowed that not to happen? $\endgroup$ Commented Feb 16, 2020 at 21:56

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It's didn't disappear. It's still around today, over 100 years later. The 1918 influenza virus is the parent virus for all the human seasonal influenza viruses that are around today, as well as for most of the swine influenza viruses out there.

In fact, the presently circulating H1N1 viruses in humans are close enough to the 1918 virus that they probably immunize against each other (Seasonal trivalent inactivated influenza vaccine protects against 1918 Spanish influenza virus infection in ferrets.).

What did happen is that the 1918 virus mutated, becoming less virulent in the process, within a year or so of entering the human population. Why? Presumably because, after infecting virtually the entire human population in its first year, there was so much population immunity that it needed to mutate a little in order to continue to infect. That is, after all, what flu viruses do.

But it continued to circulate for decades, as a very similar H1N1 virus. Also, it almost immediately infected pigs and became endemic in the swine population, only to resurface after 90 years to cause the 2009 influenza pandemic.

In 2009, persons who had lived through the first decades of the 1918 pandemic H1N1 era, especially those born before about 1950, were substantially protected from the 2009 pandemic virus by having acquired immunity to the antigenically similar H1 or N1 of the 1918 virus, or both, or to the descendant seasonal H1N1 viruses that circulated over subsequent decades. This is because the 2009 H1 gene was a 1918 viral progeny that had survived for more than 90 years, with minimal antigenic drift, in a domestic pig “time capsule.”

The Mother of All Pandemics Is 100 Years Old (and Going Strong)! (Am J Public Health. 2018 November; 108(11): 1449–1454)

In 1957 and 1968, the H1N1 virus reassorted with avian viruses to generate first H2N2 and then H3N2 viruses (the great-grandchildren of the H3N2 pandemic still circulate today). But most of the internal genes in those reassortants remained the 1918 versions.

So the 1918 flu never went away. It’s still killing hundreds of thousands of people every year. It’s just that everyone has got used to it, and thinks it’s fine and normal to have hundreds of millions of influenza cases every year.

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  • $\begingroup$ Thanks for the detailed and informative response! The reason why I'm still puzzled by all of this is that the 1918 strain was distinctive in that it killed a very large percentage of young, otherwise-healthy, of infected individuals. Somehow we're not seeing this phenomenon any more. Even if the original strain mutated to create 100 different strains, if the original strain was still around as well, wouldn't we have seen small local epidemics of it from time to time killing large percentages of the healthy adults in certain towns, etc.? $\endgroup$ Commented Feb 18, 2020 at 18:07
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    $\begingroup$ We don't know in detail why the 1918 flu was so virulent; we do know that the surface protein hemagglutinin (HA) was a significant part of it, and we know that the HA of flu viruses changes very rapidly in response to population immunity pressure. The presumption is that virulence depended on a very narrow and precise sequence, that changed as a result of adaptation to human immunity - probably because virulence per se was not an adaptive trait but was simply a side effect of other factors. $\endgroup$
    – iayork
    Commented Feb 18, 2020 at 19:28
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    $\begingroup$ nice answer! Another related question: Before 1918, there were other influenza viruses circulating? The 1918 influenza was of a zoonotic origin? Where did it came from? $\endgroup$
    – juan Isaza
    Commented Mar 26, 2020 at 4:44
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    $\begingroup$ 1918 was an avian influenza, perhaps passed through swine before infecting humans. Many strains of influenza circulated before 1918, but we don’t know much about them because we don’t have samples. There were many pandemics, presumably zoonotic, most probably avian origin but perhaps also equine $\endgroup$
    – iayork
    Commented Jul 3, 2020 at 15:54
  • $\begingroup$ Check out the below link where I have put a graph on why it killed more young people. I have also linked there a PNAS article if you're curious. biology.stackexchange.com/questions/95652/… $\endgroup$
    – m4rio
    Commented Sep 11, 2020 at 3:48
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Although the accepted answer is good and very possibly correct, I was never fully convinced by it. It describes a situation where less than a third of the world's population was infected, and yet for some reason the virus had to mutate to escape immunity to continue spreading, while the original violent strain died off. This would only make sense if the flu's R was so low that at 30% population infected, we reached herd immunity. I don't think this is plausible - unless the flu was grossly under diagnosed.

I recently read a different theory which I found more convincing:

The alternative theory posits that the flu virus often mutates in a way that does not evade immunity. In other words, being infected with one mutant protects you from the another. Now, consider that the violent virus (that appeared in the second wave of 1918) further mutated and a less violent mutant appeared. It is likely that the new mutant will have a higher R than the original. This may happen both because of a-priori reasons (namely, a less violent strain would lead more people to go out and spread it) and for a-posteriori reasons (namely, we only noticed a new strain when it has an higher R than the original). Now we have a less violent mutant with a higher R than the original violent strain. The less violent version would spread faster than the violent one, until more people are inected with the less violent one than the violent one.

Remember that we assume that catching any one of the two strains immunizes you to both, so both strains R number begin to go down, until the old strain's R is below 1 while the new one is above R. At this point the old strain goes extinct, while the new strain continues to spread for a while longer. Moreover, as the new virus is less scary, people relax all their prevention measures (masks, social isolation, etc.) so its R increases even more, allowing it to infect even more people before reaching herd immunity.

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  • $\begingroup$ Re: " It is likely that the new mutant will have a higher R than the original." Isn't this just the same as the original answer? "there was so much population immunity that it needed to mutate a little in order to continue to infect." - that is, it had a higher R. Remember, some of the human population already had resistance to the 1918 strain, whether because of prior exposure to a similar strain, or because of some gene polymorphism. $\endgroup$
    – Armand
    Commented Jul 31, 2021 at 3:56
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    $\begingroup$ The original answer posits that the new mutant has a R higher than the original's because the new mutant strain escaped immunity that the population had to the original strain. My question about this is why, under that assumption, they couldn't both serotypes continue to spread if you could get infected with both. So my new answer is that maybe you couldn't get infected with both - there was no immunity escape - getting the mild strain protected you from the violent strain (and vice versa), which can explain why today we see only the milder strain. $\endgroup$ Commented Jul 31, 2021 at 8:22
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    $\begingroup$ @Armand "they DID have some immunity already ... because of past exposure to related strains" - that's an interesting reversal of the theory I mentioned. So it's not that the mild strain evolved after the violent strain, but perhaps the opposite - the mild strain evolved first, infected most people on earth until 1918 but nobody really cared because it was a mild flu, and when in the second wave of 1918 it mutated and became violent (but still with the same antigens), it could only infect about a third of the population before herd immunity was reached and the violent strain died out. $\endgroup$ Commented Aug 1, 2021 at 7:44
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    $\begingroup$ @Armand but then the question becomes - why didn't the violent strain do what all other strains do since - mutate their antigens to evade prior immunity. The theory I mentioned might solve this question - if the violent strain was first replaced by a less violent strain with the same antigens - and only then did the antigenic drift occur. $\endgroup$ Commented Aug 1, 2021 at 7:49
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    $\begingroup$ Currently COVID-19 Omicron variant and its subvariants, each subsequent one with lower virulence, but higher transmissiblity, seem to provide real-time evidence in support of the "crowding out" theory. Note however, that the increase in transmissibility is not the only viral strain "success factor" here, because it is hard to distinguish from growing immune evasion causing re-infections. $\endgroup$
    – mirekphd
    Commented Jul 17, 2022 at 9:13

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