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‘Seasonal’ H1N1 and H3N2 influenza: Does it have a future?
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In the recorded history of pandemics caused by influenza A viruses, pandemics have been followed by yearly seasonal epidemics, caused by the same hemagglutinin type as the pandemic strain, with minor changes each year. This has continued until the next pandemic, 11 to 41 years later, with a change in hemagglutinin type (and often, but not always, a change in neuraminidase type) from the previously circulating hemagglutinin type.
There was a pandemic of H3N8 in 1901, followed by the notorious H1N1 pandemic of 1918, followed by a pandemic of H2N2 in 1957, followed by a pandemic of H3N2 in 1968, followed by an outbreak of H1N1 in 1977 (which some experts have called a pandemic and others have not considered a pandemic) and now in 2009, a pandemic of H1N1. The outbreak in 1977 was not considered a pandemic by some because it affected mainly children. This targeting of a portion of the population probably occurred because the causative H1N1 strain closely resembled the H1N1 strain causing yearly outbreaks before 1957, resulting in protective antibody and herd immunity in the adult population. The 1977 outbreak is thought by some to have resulted from the escape of a virus from a laboratory in Russia.
Much of the old information is based on serological surveys, some many years after the actual events, and therefore, the information available is imprecise as to what strains may have been circulating in low numbers. However, as far as we know, after the pandemics of 1918, 1957 and 1968, in each case, the previously circulating strain disappeared in terms of causing yearly epidemics. Unlike previous pandemics, after the 1977 outbreak, both H3N2 and H1N1 co-circulated, apparently the first time two A strains with different hemagglutinins caused interpandemic yearly outbreaks.
It is worth pointing out that the current 2009 pandemic H1N1 is the first recognized time that a pandemic has occurred with the same hemagglutinin number as the previously circulating strain. This occurred because of the emergence of a new A virus with a major difference in the hemagglutinin.
Discounting the 1977 outbreak as an odd event, and based on the past history outlined above, I believe that there is an excellent chance that after 2009, seasonal H1N1 and H3N2 (the two strains circulating before the current H1N1 pandemic strain) will disappear in terms of causing yearly epidemics. If history continues to repeat itself (as I believe it will), the only influenza A strain circulating until the next pandemic will be the current pandemic H1N1 strain, causing yearly epidemics. However, not being a betting man, I wouldn’t bet the farm on it.
Donald Kaye, MD, is a professor of medicine at Drexel University, College of Medicine in Philadelphia and associate editor of ProMED-mail.
Dr. Kaye is, of course, entirely correct in his interpretation of the historical record. It happened in 1901, again in 1918, and again in 1957. Then it happened again in 1968. In each case, the previously prevailing influenza A strain disappeared, having been replaced by the new “pandemic” strain, which became the new “seasonal” influenza strain. I don’t hesitate a moment in predicting that the previous seasonal H1N1 strain will disappear and that the pandemic H1N1 strain will take its place.
The larger question is whether the H3N2 strain will disappear as well, and I’m not at all confident about that. The historical record of serologic epidemiology suggests that it will disappear, but then I don’t completely trust the evidence from that source. It’s fine to document major shifts and the introduction of new pandemic strains, but I don’t think it is capable of showing the other strains that may have been co-circulating and causing less of a problem.
I suspect we’ll get a large clue to the answer in the next several months. If the winter/spring wave of influenza that we all expect to occur is due to H3N2, then the H3N2 strain will not disappear. If, on the other hand, it is another wave of pandemic H1N1, then I would agree with Dr. Kaye and predict that the A/H3N2 will disappear altogether for several generations before reappearing 50 to 75 years from now. H3N2 strains have been notably absent thus far this fall.
Should the pandemic H1N1 strain become our new seasonal influenza A strain, then another question quickly comes to mind: Will it mutate or drift to look more like seasonal influenza A in terms of the age distribution of both morbidity and mortality? Right now, the pandemic H1N1 strain looks more like the 1918 strain in mortality rate by age, ie, a “W” shaped curve instead of the “U” shaped curve typical of seasonal influenza. The attack rate in the elderly is still quite low, but those few who get the disease fare poorly.
Theodore Eickhoff, MD, is professor emeritus in the division of infectious disease at the University of Colorado Health Sciences Center in Denver.