Influenza Pandemics of 1918 and 2009

Table 1. Pandemics caused by influenza A virus in the past century.
Year	Subtype	Resulting pandemic	Estimated deaths (millions)
1918	H1N1	Devastating	50–100
1957	H2N2	Moderate	1–4
1968	H3N2	Mild	1–4
2009	H1N1	Mild	0.5–1

Table 2. Comparative features of the 1918 and 2009 influenza pandemics.
Basis of comparison	1918 (H1N1) pandemic	2009 (H1N1) pandemic
Isolation of the strain	Could not be isolated	Isolated soon after detection
Genetic basis	De novo genetic adaptation of avian virus into humans	Genetic reassortant of avian, human and swine influenza strains
Pathogenicity	Highly pathogenic	Moderately pathogenic
Low incidence rates in individuals >65 years of age	Observed due to first exposure to antigenetically related H1N1 virus	Observed due to first exposure to antigenetically related H1N1 virus
Hemagglutinin structure	Tip of hemagglutinin is bald (nonglycosylated)	Tip of hemagglutinin is bald (nonglycosylated)
Antiviral drugs	Not available at that time	Neuraminidase inhibitors were recommended (within 48 h of illness onset)
Vaccine	Not developed	Developed within 6 months of detection

The 1918 (H1N1) Pandemic

The 1918 (H1N1) pandemic killed an estimated 50–100 million people.
Although the first wave originated in the USA, it is still difficult to assign a geographical point of origin due to its simultaneous appearance in other parts of the world.
Exhibited a W-shaped mortality pattern associated with an overwhelming number of deaths in young adults.

The 2009 (H1N1) Pandemic

Comparative Features of the 1918 & 2009 Influenza Pandemics

Age shift during the 1918 pandemic was extreme, in which the majority of deaths occurred among individuals under 45 years of age, sparing people above this age.
During the 2009 influenza pandemic, approximately 75% of confirmed cases were below 30 years of age and fewer than 3% of the cases were in individuals ≥65 years of age.
Extensive organ involvement was an outstanding feature of the 1918 H1N1 pandemic. In comparison with the 1918 virus infection, the clinical features of the 2009 pandemic were milder.
The crystal structure of the hemagglutinin of both the viruses is similar, especially within the Sa antigenic site.
Compared with seasonal influenza outbreaks, the overall impact of the 2009 H1N1 pandemic was lower in adults ≥65 years of age. This is possibly due to the presence of protective cross-reactive antibodies developed through childhood exposure to the 1918 pandemic virus, with which it shares antigenic similarity.

Conclusion

These two pandemics teach us a lesson: that influenza pandemics are unpredictable and are prone to delivering surprises.
There are gaps that need to be addressed in influenza surveillance in humans and other animals.
We must remain vigilant and continue to monitor the epidemiology and health burden of the A/H1N1 influenza virus.