"In the late 1950s and 1960s, Francis and others hypothesized that only a very few naturally occurring influenza A virus subtypes had the ability to cause pandemics. These few virus subtypes reappeared in regular cycles determined by the lifespans of human birth cohorts exposed to them and rendered immune to them. This hypothesis has not yet been refuted by the past century of influenza experience. Extending observations back in time to the century before 1918, epidemiological and archaeserological evidence is consistent with the possibility that pandemics between the 1830s and 1889 may, like those of the past century, have only expressed HA subtypes H1, H2, or H3. Moreover, anecdotal observations going back to the mid-1700s are consistent with such HA recycling. If pandemics are explained by recycling of only a few influenza HA and NA subtypes, our efforts to develop preventive vaccines and our viral surveillance strategies need to be targeted accordingly. We currently do not know whether pandemic influenza threats of the future will be few in number and restricted in severity, or multitudinous and deadly."
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Influenza
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