Influenza epidemics have killed millions. Although most are probably unrecorded, having occurred long ago, the best known and possibly the most deadly was the 1918 H1N1 Flu Pandemic better known as the Spanish Flu. From 1918 to 1920, some 50 to 100 million people died, which was about 3% to 6% of the world’s population at the time. By comparison, 15 million soldiers and civilians perished during World War I. With a current world population of 7 billion people, if the Spanish Flu occurred today, it could potentially kill 210 to 420 million–more than the entire US population.
Influenza A subtypes are identified by the structure of two surface proteins: hemagglutinin (H) and neuraminidase (N). There are 16 H subtypes and 9 N subtypes, although only H1, H2, and H3 are normally found in humans.
The seasonal flu is not a benign disease and causes about 40,000 deaths per year in the US with over 200,000 hospitalizations. It tends to affect the very young and very old. In contradistinction, the Spanish Flu affected young, healthy adults.
H1N1 strains are different genetically, which make their virulence different from each other. The exact strain of the Spanish Flu H1N1 is unknown. While the virus was replicated from frozen tissue samples from victims, no actual viral samples are known to have survived although there is some dissent on this fact.
Unique to the 1918 pandemic was the subsequent encephalitis lethargica (EL) epidemic first described in Austria by the mechanical engineer-turned-neurologist, Constantin von Economo. EL was also called “sleeping sickness,” although many other unrelated sleeping sicknesses occur. Various theories suggest that EL was not caused by a separate virus but was, instead, an autoimmune response to influenza with antibodies that were targeted against deep neuronal clusters called basal ganglia. There has never been another EL epidemic since that time.